Mechanistic studies further showed that such metabolic inflammation is related to the induction of various intracellular stresses such as mitochondrial oxidative stress, endoplasmic reticulum (ER) stress, and autophagy defect under prolonged nutritional excess
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shared by wheelchairindia9 on 22 Mar 16
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Tynor Walker Boot - 0 views
www.wheelchairindia.com/...Tynor-Walker-Boot
Tynor Walker Boot Walker Boot Walker Boots Tynor Walker Tynor Walkers tynor walking boot walker boot tynor
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Tynor Walker Boot is designed by the Tynor to rehabilitate the person after injury or fracture. It allows easy movement as well as supports the ankle and leg. This can be a great substitute for cast and also useful during early cast removal. It can also be used during sprain in the foot and this walker gives great relief to the pain. It can easily do any mild activity. It also works for the persons with a lower leg and will give an equal level of the lower feet as well as reduces the pressure. It effectively enclosed the muscles of the leg or foot during the fracture and gives comfort without disturbing the recovery process. This walker boot is made up from the good quality material. It has Aluminum lateral bars that are corrosion free. It is light in weight and provides enhanced mobility. It gives sturdy support to feet and leg. Its Hook Loop system allows to adjust it according to the comfort. It is also infused with Foam liner and Pad set that gives soft feet and also provides great support. It is available in different sizes. Tynor Walker Boot Tynor Walker Boot is designed for rehabilitation after injury, fracture , sprains or surgery of foot, ankle or lower leg. The boots provide support to the ankle and leg without inhibiting mobility. They can be a substitute for cast or can be used in case of early cast removal. With a wider rocker bottom, these boots promote a natural gait, reduced plantar pressure, enhanced stability and comfort to the lower leg. Light weight. Sturdy Support. Enhanced mobility. Maintains normal gait. Tynor Walker Boot Features Moulded foot Improves gait Rocker sole-helps in easy ambulation Offers stabilization of the foot ankle and the lower leg Comfortable positioning and protection of the foot Aluminum lateral bars Rigid support-Improved immobilization of the ankle and the lower leg Malleable, shape can be customized for better fitting and support Foam liner and Pad set Ensure extreme comfort Ensure per
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shared by wheelchairindia9 on 31 Mar 16
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Leg Traction Brace - 0 views
www.wheelchairindia.com/...Tynor-Leg-Traction-Brace
Tynor Leg Traction Brace Leg Traction Brace Leg Traction Braces Leg Traction Brace Online Leg Traction Brace Online India Leg Traction Brace Price Buy Leg Traction Brace
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Tynor Leg Traction Brace is basically designed to provide traction to the leg. It works well even on the weak or geriatric skin. It ensures proper compression of the leg and provides traction. It is made of three layered polyurethane fabric which makes it soft and comfortable to use. The innermost layer gives the required friction for faster recovery. It is augmented with hook and loop closures to make it convenient to put on and remove. It does not require any adhesion. It provides cushion like support to the leg and relieves it from pain. It also prevents the bone from getting fractured and any muscle pull. It does not cause any peeling of skin and any rash or allergy on skin. It distributes the pressure exerted on the leg evenly. Tynor Leg Traction Brace Leg traction brace is a traction halter applied to the leg for below knee traction. It offers a distinct advantage of a very large holding surface area, ease of application and removal, reuse and patient comfort. Easy application & removal. Can be used for geriatric/ weak skin. Ideal for sensitive skins. Easy monitoring. Distributes pressure evenly. Tynor Leg Traction Brace Features Three-layered PU bonded fabric offers: Soft feel and plush looks through the top layer. Comfortable cushioning through the middle Polyurethane layer. Inner layer provides good frictional characteristics. Multiple hook loop closures Ensure controlled compression. Easy application and removal No loosening, less monitoring Large skin contact area Ensures no vaso-constriction. Eliminates need of an adhesive. Convenient and quick to apply Ensures no skin peeling. Ideal for weak or geriatric skins Tynor Rib Belt Rib belt is applied to the thoracic and upper abdominal region to compress and bind the rib cage during rib fractures and postoperative care, while allowing sufficient flexibility for comfortable breathing. Extra porous. With splinting pad. No buckling or rolling over. Controlled compression
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shared by wheelchairindia9 on 06 Apr 16
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Weight Cuff - 0 views
www.wheelchairindia.com/...Tynor-Weight-Cuff
The Best Exercise for Strengthening Shoulders improve muscle strength Iron pellets filled cuff multiple sclerosis patients rehab therapy programs allowing sufficient flexibility
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Tynor Weight Cuff Tynor Weight cuffs are used to exercise ailing joints to build strength and aid recovery. Tynor Weight Cuff is flexible and cushion, so it does not injure. Recommended for use to improve muscle tone, muscle mass, strength and stamina. Tynor Weight Cuff Features Offers 1 kg resistance when wrapped around Weight is wrapped in comfortable and soft fabric Used to build muscles, flexibility or to lose weight Can be secured easily around to prevent injuries or accidents Cuff is safe to be used during everyday activities as well Tynor Weight Cuff Measurements Sizes Available: 1/2 Kg / 1Kg / 2 Kg
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shared by wheelchairindia9 on 06 Apr 16
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Chest Binder - 0 views
www.wheelchairindia.com/...Tynor-Chest-Binder
The Best Exercise for Strengthening Shoulders improve muscle strength Iron pellets filled cuff multiple sclerosis patients rehab therapy programs allowing sufficient flexibility
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Tynor Chest Binder Chest Binder is applied to the thoracic region to compress and bind the rib cage and provide splinting to the sternum while allowing sufficient flexibility for comfortable breathing. Anatomic chest pad. Controlled compression. Optimum chest splinting. Soft feel. Tynor Chest Binder Features 50 mm thick PUF pad hold and binds the fractured sternum without compromising on patient comfort. Strong elastic band gives good grip and helps in equidistribution of pressure. Reduces post operative pain and discomfiture. Facilitates phlegm expulsion after cardio thoracic surgery. Tynor Chest Binder Measurements Measure circumference around the chest.
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shared by hadiyasafdar on 12 Jan 17
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Rhinoplasty Surgery,Tips, Recovery, Risks and More - 0 views
dubaicosmeticsurgeryclinics.blogspot.com/...urgerytips-recovery-risks.html
RhinoplastyDubai NoseReshapeDubai NosesurgeryDubai Noseplasticsurgery Rhinoplastysharjah NosejobDubai
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Rhinoplasty is a cosmetic surgery in which the size and shape of your nose is altered for both aesthetic and functional reasons. Rhinoplasty involves your surgeon to make changes to your nose according to your requirements ensuring these changes compliment other facial features and to solve the functional issues of the nose.click here to read about Helpful tips to find the best nose reshaping surgery.
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shared by wheelchairindia9 on 14 Mar 16
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Tynor Knee Cap Comfeel - 0 views
www.wheelchairindia.com/...Tynor-Knee-Cap-Comfeel
Tynor Knee Cap Comfeel Knee Cap Comfeel knee cap comfeel support tynor knee comfeel tynor knee cap comfeel brace knee caps comfeel
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Tynor Knee Cap Comfeel Knee cap comfeel is a next generation tubular product knitted on a 3 dimensional computer controlled circular looms to provide mild compression, warmth and support to the knee joint. It is used to allay pain and inflammation, generally associated with old age, arthritis or injury. Soft Patella Fine grip at the edges Four way stretch Uniform compression Simple pull on application. Tynor Knee Cap Comfeel Features Anatomically shaped and reduced compression on patella No Chondromalacia on prolonged use Better compression and grip Easy knee movement Improved comfort Bi-layered, cotton on the inside , a dermophillic interphase Enhanced comfort Better sweat absorption Better patient compliance. Bilayered, nylon on the outside Ensures long life Excellent aesthetics Color fastness. Four-way stretchable fabric Effective compression Enhanced comfort. Two layered with interwoven air space Retains body heat effectively. Speeds up healing Allays pain. Tynor Knee Cap Comfeel Measurements Measure circumference around mid thigh - approx 6 inches above knee Size Chart - Size Inches CM Small 14.8-17.2 37-43 Medium 17.2-19.6 43-49 Large 19.6-22 49-55 XL 22-24.4 55-61
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shared by wheelchairindia9 on 15 Mar 16
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Tynor Ankle Brace - 0 views
www.wheelchairindia.com/...Tynor-Ankle-Brace
Tynor Ankle Brace ankle brace ankle braces ankle support brace best ankle brace best ankle support ankle support braces brace ankle tynor ankle braces
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Tynor Ankle Brace Ankle brace is designed to support, stabilize, and limit the range-of-motion of the ankle joint. In injury, or offer protection to people who are prone to ankle injuries. It uses the triple action of straps, laces and rigid lateral natomical splints to provide optimal ankle stabilization. Rigid Splinting Fits left & right. Easy to wear Controlled compression. Comfortable sung fit. Tynor Ankle Brace Features Triple stabilization Splint ensure strong immobilization Lace offers regional tightening, firm grip and good fitting. "Figure of eight Tynor Ankle Brace Measurements Measure circumference approx 2 inches above the ankle joint. Size Chart- Size Inches CM Small 7.2-8.4 18-21 Medium 8.4-9.6 21-24 Large 9.6-10.8 24-27 XL 10.8-12 27-30
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shared by wheelchairindia9 on 17 Mar 16
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Tynor Ankle Splint - 0 views
www.wheelchairindia.com/...Tynor-Ankle-Splint
Tynor Ankle Splint Ankle Splint ankle splints ankle support splints Ankle Splint braces ankle support splint ankle brace splint tynor ankle support splint
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Ankle Splint Ankle Splint is designed to immobilize, support and stabilize the ankle joint in injury, or offer protection to people prone to ankle injuries. Rigid exoskeleton shell design gives better protection and control of the inversion or aversion of the ankle. Rigid immobilization Foam cushioning One size, that fits all Anatomical Easy to clean. Ankle Splint Features Unique figure of eight gripping Effective control on inversion & eversion movement of ankle Most effective gripping around ankle. Enhances comfort and walking pleasure Large enough room for ankle Unconventional, swollen or distorted ankles can be accommodated No compression hot spots on the ankle , so enhances comfort to injured ankle Reduces chances of sports related injuries in recurrent ankle problems Quick healing and better recovery of the fully immobilized ankle Molded Ethafoam Foam Pad Provides optimal compression and pressure Good cushioning , enhances comfort Skin friendly Ergonomic design Light in weight - enhance compliance Bilateral symmetry - can be used for either ankle Neoprene sleeves - good cushioning ,reduce pressure of gripping straps One size fits all Molded splint with perfect anatomy Pleasing aesthetics Sleek can be used inside the shoe Effective immobilization. Ankle Splint Measurements Measure circumference approx 2 inches above the ankle joint. Size Chart - Size Inches CM Universal 7.2-12 18-30
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shared by wheelchairindia9 on 23 Mar 16
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Wrist Brace with Double Lock - 0 views
www.wheelchairindia.com/...r-Wrist-Brace-with-Double-Lock
Tynor Wrist Brace with Double Lock wrist brace with double lock double lock brace wrist Wrist Brace with Double Lock online wrist brace with double lock online india wrist brace with double lock price buy wrist brace with double lock wrist brace with doub
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Tynor Wrist Brace with Double Lock Wrist brace with double lock is designed to support, protect and partially immobilize the wrist. It compresses the area and retain the body heat to allay local pain and inflammation. Extra grip. Extra porous Controlled compression. Easy application. Tynor Wrist Brace with Double Lock Features High quality, striped elastic webbing Strong and durable Porous and comfortable High modulus of elasticity- Retains shape and size for a long time. Excellent compressive strength, better support Hook loop Double locking Easy to apply and remove Ensures optimal compression Better fitting and universal sizing. Tynor Wrist Brace with Double Lock Measurements Measure circumference evenly around the wrist joint
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shared by wheelchairindia9 on 26 Mar 16
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Tynor Wrist Splint Ambidextrous - 0 views
www.wheelchairindia.com/...ynor-Wrist-Splint-Ambidextrous
Tynor Wrist Splint Ambidextrous wrist splint ambidextrous ambidextrous wrist splint ambidextrous wrist support ambidextrous wrist splint support wrist splint ambidextrous online buy wrist splint ambidextrous
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Tynor Wrist Splint Ambidextrous Applications Early cast removal. Fracture management. Post surgical protection and rehabilitation. Rheumatic disease of the wrist and arthritic hand positioning. Bursitis, Tendonitis, Tensosynovitis. Psychological assurance. Post extensor tendon repair surgery. Conservative management of keinbock's disease. Sprains and strains. Tynor Wrist Splint Ambidextrous Features Customizable Splints. Controlled compression. Anatomical thumb opening. Fits both left and right hand. Tynor Wrist Splint Ambidextrous Measurements Measure circumference at a distance 6" from the wrist along the arm
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shared by wheelchairindia9 on 25 Mar 16
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Tynor Cervical Collar Hard Adjustable - 0 views
www.wheelchairindia.com/...ervical-Collar-Hard-Adjustable
Tynor Cervical Collar Hard Adjustable Cervical Collar Hard Adjustable hard cervical collar adjustable cervical collar cervical collar adjustable tynor cervical collar hard hard neck collar
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Tynor Cervical Collar Hard Adjustable Cervical Collar Hard Adjustable is used for supporting, immobilizing or adjusting the neck in the flexion, extension, or hyperextension position. Recommended where a rigid immobilization of the cervical region is required. Anatomical shape. Comfortable edge padding. Adjustable height. Slight weight. Latex free. Tynor Cervical Collar Hard Adjustable Features Edge padding by ethafoam Better cushioning and comfort long functional life Light in weight No leaching no allergy Better cushioning and comfort Anatomically designed with height adjustment Ensures perfect fitting Improves immobilsation Enhances comfort Perforated Better ventilation Enhances comfort Better patient compliance. High quality PE Sheet Ensures rigid support Long life of the collar Improves aesthetics. Tynor Cervical Collar Hard Adjustable Measurements Measure distance between edge of sternum and lower jaw with neck in extension position.
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shared by wheelchairindia9 on 26 Mar 16
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Tynor Elastic Wrist Splint - 0 views
www.wheelchairindia.com/...Tynor-Elastic-Wrist-Splint
Tynor Elastic Wrist Splint elastic wrist splint buy wrist splint elastic wrist splint online india elastic wrist splint india buy tynor elastic wrist splint elastic wrist splint tynor best tynor elastic wrist splint
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Tynor Elastic Wrist Splint Tynor Elastic Wrist Splint is designed to immobilize and provide firm support to hand and wrist in various orthopedic conditions. It maintains the wrist in the dorsi flexion functional position while allowing full range of motion to fingers and thumb. The splint can be removed to permit, therapy sessions, washing and hygiene. Malleable Splint. Perfect Immobilization Controlled compression. Anatomical thumb opening. Tynor Elastic Wrist Splint Features High quality Elastic Webbing Strong and durable Porous and comfortable High modulus of elasticity-- Retains shape and size for a long time. Removable, Aluminum Splints Customized fitting Required degree of dorsi-flexion can be achieved Very good grip and immobilization Hook loop closures Easy to apply and remove Ensures optimal compression. Built in opening for thumb abduction Better pain relief and healing. Thumb remains relaxed, no fatigue mproves comfort Tynor Elastic Wrist Splint Measurements Measure circumference evenly around the wrist
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shared by wheelchairindia9 on 16 Mar 16
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Tynor Exercising Ball - 0 views
www.wheelchairindia.com/...Tynor-Exercising-Ball
Tynor Exercising Ball Exercising Ball tynor exercising ball online exercising ball tynor tynor exercising ball online india tynor exercising ball price buy tynor exercising ball Exercising Balls
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Tynor Exercising Ball Exercising ball is an excellent physiotherapy device to provide a pleasurable exercise plan for the hand, wrist, forearm and the fingers Safe and inert. High patient compliance. Excellent resilience for a long functional life . Compatible in thermal/hydrotherapy. Tynor Exercising Ball Features Ergonomic design and materials Two resistances available- Ortho (hard) & Neuro (soft) Compatible for thermal/hydrotherapy Flexible and pleasurable exercise schedules can be planned Better compliance Inert PU material, safe to use Excellent resilience, offers longer life. Tynor Exercising Ball Measurements Sizes Available: OR / NR
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shared by wheelchairindia9 on 17 Mar 16
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Tynor Restrainer - 0 views
www.wheelchairindia.com/...Tynor-Restrainer
Tynor Restrainer Restrainer Tynor Tynor Restrainer price Tynor Restrainer online Tynor Restrainer online india buy Tynor Restrainer Tynor Restrainer sale
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Tynor Restrainer Applications To manage combative or disoriented patient. Manage post anesthesia delirium. Patients with head injuries or recovering from seizures. Schizophrenia, mental illness, dementia, or side effects from their treatment. To limit the body movement. Maintain a particular position. Tynor Restrainer Features Cushiony & comfortable. Easy to tie and open. Strong and durable. Fits left, right, wrist & ankle. Tynor Restrainer Measurements Size Chart - Size Inches CM Universal 5-9.5 12.5-23.8
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shared by wheelchairindia9 on 17 Mar 16
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Tynor Cervical Collar Soft - 0 views
www.wheelchairindia.com/...Tynor-Cervical-Collar-Soft
Tynor Cervical Collar Soft cervical collar neck braces soft cervical collar soft neck brace cervical soft collar cervical collar soft Cervical Collar Soft tynor tynor soft cervical collar
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Tynor Cervical Collar Soft Cervical collar soft is used for supporting the neck and protecting it against jerks impacts and vibrations. Recommended where a partial or controlled immobilization of the cervical region is required. Ultimate comfort. Partial immobilization. Optimal support. Excellent aesthetics. Absorbs impact. Tynor Cervical Collar Soft Features Soft polyurethane Provides unmatched comfort, used as prophylactic collar, reduces pain and provides comfortable support during traveling. Covered with hypoallergenic cotton stockinet. Better patient comfort, no allergy or rash even to sensitive skin, better compliance No hard, bony reinforcement Improves patient comfort, particularly recommended for geriatric patients, excellent for prolonged use. Anatomical design Uniform support to the mandible, effective action and better fit, better comfort. Perforated collar body Improved ventilation, more patient comfort, better compliance.
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shared by wheelchairindia9 on 23 Mar 16
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Tynor Ankle Binder - 0 views
www.wheelchairindia.com/...Tynor-Ankle-Binder
Get Happy Feet With The Right Walking Boots orthopedic walking boot boot type walkers decrease pain and edema comfort to the lower leg rocking motion of the foot boots provide support to the ankle
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The boot type walkers can be provided in a fixed mode or with ankle joints to provide articulation. Pneumatic support is also available. The brace has a lightweight, durable, semi rigid shell that will support the limb and provide protection. Incorporated are medial and lateral uprights, heel and rocker sole. Closure is achieved with Velcro. The strapping system provides full circumferential compression of the limb. The breathable fiber liner is washable. The articulated boot allows range of motion (ROM) usually from approximately 20 degrees dorsiflexion to 40 degrees plantar flexion. Tynor Walker Boot is designed by the Tynor to rehabilitate the person after injury or fracture. It allows easy movement as well as supports the ankle and leg. This can be a great substitute for cast and also useful during early cast removal. It can also be used during sprain in the foot and this walker gives great relief to the pain. It can easily do any mild activity. It also works for the persons with a lower leg and will give an equal level of the lower feet as well as reduces the pressure. It effectively enclosed the muscles of the leg or foot during the fracture and gives comfort without disturbing the recovery process. This walker boot is made up from the good quality material. It has Aluminum lateral bars that are corrosion free. It is light in weight and provides enhanced mobility. It gives sturdy support to feet and leg. Its Hook Loop system allows to adjust it according to the comfort. It is also infused with Foam liner and Pad set that gives soft feet and also provides great support. It is available in different sizes. Tynor Walker Boot is designed for rehabilitation after injury, fracture , sprains or surgery of foot, ankle or lower leg. The boots provide support to the ankle and leg without inhibiting mobility. They can be a substitute for cast or can be used in case of early cast removal. With a wider rocker bottom, these boots promote a natural gait, reduced
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shared by wheelchairindia9 on 02 Apr 16
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Hernia Belt - 0 views
www.wheelchairindia.com/...Tynor-Hernia-Belt
Tynor Hernia Belt Hernia Belt hernia support belt Abdominal Hernia Belt belt hernia Hernia abdominal support Hernia abdominal support belt tynor hernia hernia support belts Hernia Belts
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Tynor Hernia Belt Hernia belt offers a gentle and constant relief from reducible inguinal hernia by providing adjustable and comfortable pressure to the hernia. On wearing the belt the occurrence of herniation gets eliminated. Tynor hernia belt is available in skin color, can be worn inconspicuously under clothing. Moulded foam pads. Adjustable leg and abdominal strap. Soft and skin friendly materials. Controlled pressure. Tynor Hernia Belt Features Anatomic pads Presses the inguinal aperture at the appropriate angle, enhances the effectiveness. Molded out of special grade ethafoam Appropriate hardness, light weight, smooth and comfortable. Grey color product Can be worn inconspaciously under cloth, aesthetically pleasing. Soft and dermophilic materials No rash no allergy, very comfortable, improve compliance. Adjustable pelvic and leg straps One size fits a large population, controlled & customized pressure possible. Tynor Hernia Belt Measurements Measure circumference around the waist 2 inches below the navel.
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shared by wheelchairindia9 on 02 Apr 16
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Tummy Trimmer Abdominal Belt Supports - 0 views
www.wheelchairindia.com/...ummy-Trimmer-or-Abdominal-Belt
Tynor Tummy Trimmer or Abdominal Belt Tummy Trimmer Abdominal Belt Supports tummy trimmer belt tummy trimming belt abdominal support belt 8 tynor tummy trimmer support belt tummy trimmer abdominal belts
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Tynor Tummy Trimmer or Abdominal Belt Tummy Trimmer/Abdominal belt supports and compresses the abdominal muscles for waist line reduction and is used as a post operative or post delivery aid. Perfect elasticity. Breathable materials. Dermophillic. No rolling over, no buckling. Tynor Tummy Trimmer or Abdominal Belt Features Extra porous three panel webbing improves ventilation and comfort of the patient. Broad hook and loop tape panel offers better holding and size adjustability. Optimal compression, tones up abdominal muscles following surgery, CS or delivery. Optimal compression binds surgical incisions of abdomen & chest, improves healing. Holds the incision, provide analgesic effect during sudden movements or coughing. Special nylon reeves prevent rolling over of belt. Can be used in ventral hernia. Tynor Tummy Trimmer or Abdominal Belt Measurements Tummy Trimmer / Abdominal Belt 8 Measure circumference around the waist immediately below the navel.
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shared by Nathan Goodyear on 09 Jul 13
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Inflammatory cause of metabolic syndrome via brain stress and NF-κB - 0 views
www.ncbi.nlm.nih.gov/...PMC3314172
metabolic syndrome TLR cytokines hypothalamus brain neurology metabolic syndrome NF-kappaB DIO diet induced obesity over nutrition nutrition inflammation
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intracellular stress-inflammation process for metabolic syndrome has been established in the central nervous system (CNS) and particularly in the hypothalamus
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the CNS and the comprised hypothalamus are known to govern various metabolic activities of the body including appetite control, energy expenditure, carbohydrate and lipid metabolism, and blood pressure homeostasis
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Reactive oxygen species (ROS) refer to a class of radical or non-radical oxygen-containing molecules that have high oxidative reactivity with lipids, proteins, and nucleic acids
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a large measure of intracellular ROS comes from the leakage of mitochondrial electron transport chain (ETC)
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Another major source of intracellular ROS is the intentional generation of superoxides by nicotinamide adenine dinucleotide phosphate (NADPH) oxidase
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there are other ROS-producing enzymes such as cyclooxygenases, lipoxygenases, xanthine oxidase, and cytochrome p450 enzymes, which are involved with specific metabolic processes
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To counteract the toxic effects of molecular oxidation by ROS, cells are equipped with a battery of antioxidant enzymes such as superoxide dismutases, catalase, peroxiredoxins, sulfiredoxin, and aldehyde dehydrogenases
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intracellular oxidative stress has been indicated to contribute to metabolic syndrome and related diseases, including T2D [72; 73], CVDs [74-76], neurodegenerative diseases [69; 77-80], and cancers
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intracellular oxidative stress is highly associated with the development of neurodegenerative diseases [69] and brain aging
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mitochondrial dysfunction in hypothalamic proopiomelanocortin (POMC) neurons causes central glucose sensing impairment
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Endoplasmic reticulum (ER) is the cellular organelle responsible for protein synthesis, maturation, and trafficking to secretory pathways
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ER stress has been associated to obesity, insulin resistance, T2D, CVDs, cancers, and neurodegenerative diseases
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under environmental stress such as nutrient deprivation or hypoxia, autophagy is strongly induced to breakdown macromolecules into reusable amino acids and fatty acids for survival
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intact autophagy function is required for the hypothalamus to properly control metabolic and energy homeostasis, while hypothalamic autophagy defect leads to the development of metabolic syndrome such as obesity and insulin resistance
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prolonged oxidative stress or ER stress has been shown to impair autophagy function in disease milieu of cancer or aging
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TLRs are an important class of membrane-bound pattern recognition receptors in classical innate immune defense
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overnutrition constitutes an environmental stimulus that can activate TLR pathways to mediate the development of metabolic syndrome related disorders such as obesity, insulin resistance, T2D, and atherosclerotic CVDs
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Isoforms TLR1, 2, 4, and 6 may be particularly pertinent to pathogenic signaling induced by lipid overnutrition
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hypothalamic TLR4 and downstream inflammatory signaling are activated in response to central lipid excess via direct intra-brain lipid administration or HFD-feeding
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overnutrition-induced metabolic derangements such as central leptin resistance, systemic insulin resistance, and weight gain
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these evidences based on brain TLR signaling further support the notion that CNS is the primary site for overnutrition to cause the development of metabolic syndrome.
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circulating cytokines can limitedly travel to the hypothalamus through the leaky blood-brain barrier around the mediobasal hypothalamus to activate hypothalamic cytokine receptors
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significant evidences have been recently documented demonstrating the role of cytokine receptor pathways in the development of metabolic syndrome components
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entral administration of TNF-α at low doses faithfully replicated the effects of central metabolic inflammation in enhancing eating, decreasing energy expenditure [158;159], and causing obesity-related hypertension
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Resistin, an adipocyte-derived proinflammatory cytokine, has been found to promote hepatic insulin resistance through its central actions
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both TLR pathways and cytokine receptor pathways are involved in central inflammatory mechanism of metabolic syndrome and related diseases.
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In quiescent state, NF-κB resides in the cytoplasm in an inactive form due to inhibitory binding by IκBα protein
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IKKβ activation via receptor-mediated pathway, leading to IκBα phosphorylation and degradation and subsequent release of NF-κB activity
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Research in the past decade has found that activation of IKKβ/NF-κB proinflammatory pathway in metabolic tissues is a prominent feature of various metabolic disorders related to overnutrition
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it happens in metabolic tissues, it is mainly associated with overnutrition-induced metabolic derangements, and most importantly, it is relatively low-grade and chronic
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this paradigm of IKKβ/NF-κB-mediated metabolic inflammation has been identified in the CNS – particularly the comprised hypothalamus, which primarily accounts for to the development of overnutrition-induced metabolic syndrome and related disorders such as obesity, insulin resistance, T2D, and obesity-related hypertension
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evidences have pointed to intracellular oxidative stress and mitochondrial dysfunction as upstream events that mediate hypothalamic NF-κB activation in a receptor-independent manner under overnutrition
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In the context of metabolic syndrome, oxidative stress-related NF-κB activation in metabolic tissues or vascular systems has been implicated in a broad range of metabolic syndrome-related diseases, such as diabetes, atherosclerosis, cardiac infarct, stroke, cancer, and aging
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intracellular oxidative stress seems to be a likely pathogenic link that bridges overnutrition with NF-κB activation leading to central metabolic dysregulation
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overnutrition is an environmental inducer for intracellular oxidative stress regardless of tissues involved
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excessive nutrients, when transported into cells, directly increase mitochondrial oxidative workload, which causes increased production of ROS by mitochondrial ETC
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oxidative stress has been shown to activate NF-κB pathway in neurons or glial cells in several types of metabolic syndrome-related neural diseases, such as stroke [185], neurodegenerative diseases [186-188], and brain aging
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central nutrient excess (e.g., glucose or lipids) has been shown to activate NF-κB in the hypothalamus [34-37] to account for overnutrition-induced central metabolic dysregulations
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overnutrition can present the cell with a metabolic overload that exceeds the physiological adaptive range of UPR, resulting in the development of ER stress and systemic metabolic disorders
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chronic ER stress in peripheral metabolic tissues such as adipocytes, liver, muscle, and pancreatic cells is a salient feature of overnutrition-related diseases
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recent literature supports a model that brain ER stress and NF-κB activation reciprocally promote each other in the development of central metabolic dysregulations
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when intracellular stresses remain unresolved, prolonged autophagy upregulation progresses into autophagy defect
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autophagy defect can induce NF-κB-mediated inflammation in association with the development of cancer or inflammatory diseases (e.g., Crohn's disease)
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The connection between autophagy defect and proinflammatory activation of NF-κB pathway can also be inferred in metabolic syndrome, since both autophagy defect [126-133;200] and NF-κB activation [20-33] are implicated in the development of overnutrition-related metabolic diseases
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Both TLR pathway and cytokine receptor pathways are closely related to IKKβ/NF-κB signaling in the central pathogenesis of metabolic syndrome
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Overnutrition, especially in the form of HFD feeding, was shown to activate TLR4 signaling and downstream IKKβ/NF-κB pathway
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TLR4 activation leads to MyD88-dependent NF-κB activation in early phase and MyD88-indepdnent MAPK/JNK pathway in late phase
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these studies point to NF-κB as an immediate signaling effector for TLR4 activation in central inflammatory response
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TLR4 activation has been shown to induce intracellular ER stress to indirectly cause metabolic inflammation in the hypothalamus
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central TLR4-NF-κB pathway may represent one of the early receptor-mediated events in overnutrition-induced central inflammation.
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cytokines and their receptors are both upstream activating components and downstream transcriptional targets of NF-κB activation
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central administration of TNF-α at low dose can mimic the effect of obesity-related inflammatory milieu to activate IKKβ/NF-κB proinflammatory pathways, furthering the development of overeating, energy expenditure decrease, and weight gain
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the physiological effects of IKKβ/NF-κB activation seem to be cell type-dependent, i.e., IKKβ/NF-κB activation in hypothalamic agouti-related protein (AGRP) neurons primarily leads to the development of energy imbalance and obesity [34]; while in hypothalamic POMC neurons, it primarily results in the development of hypertension and glucose intolerance