A subsequent study by Yuan et al. showed that Tnf treatment of 3T3L1 adipocytes induces insulin resistance and that this could be prevented by pretreatment of cells with aspirin
Activation of the Tnf receptor results in stimulation of NFκB signaling via Ikkb
the percentage of macrophages in a given adipose tissue depot is positively correlated with adiposity and adipocyte size
Il-10 is an anti-inflammatory cytokine produced by macrophages and lymphocytes
Il-10 exerts its anti-inflammatory activity by inhibiting Tnf-induced NFκB activation by reducing IKK activity [38]
adipose tissue macrophages are responsible for nearly all adipose tissue Tnf expression and a significant portion of Nos2 and Il6 expression
One theory holds that the expansion of adipose tissue leads to adipocyte hypertrophy and hyperplasia and that large adipocytes outstrip the local oxygen supply leading to cell autonomous hypoxia with activation of cellular stress pathways
The use of the anti-inflammatory compounds, salicylate and its derivative aspirin, for treating symptoms of T2DM dates back over 100 years
elevated levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6) and interleukin (IL-8) have all been reported in various diabetic and insulin resistant states
overnutrition and obesity are often accompanied by elevations in tissue and circulating FFA concentrations, and saturated FFAs can directly activate pro-inflammatory responses
Adipokines such as resistin, leptin and adiponectin, which are secreted by adipocytes, can also affect inflammation and insulin sensitivity
In skeletal muscle insulin promotes glucose uptake by stimulating translocation of the GLUT4 glucose transporter
macrophages are also capable of undergoing a phenotypic switch from an M1 state, which was defined as the “classically activated” pro-inflammatory macrophage, to the M2 state or the “alternatively activated” non-inflammatory cell
saturated fatty acids are the most potent inducers of this inflammatory response
Several inducers of insulin resistance, including FFAs, pro-inflammatory cytokines and oxidative stress, activate the expression of Nos2, the gene that encodes iNOS (reviewed in [33]
Adipose tissue insulin signaling results in decreased hormone sensitive lipase activity and this anti-lipolytic effect inhibits free fatty acid (FFA) efflux out of adipocytes.
In the liver, insulin inhibits the expression of key gluconeogenic enzymes and, therefore, insulin resistance in liver leads to elevated hepatic glucose production
elevated JNK activity in liver, adipose tissue and skeletal muscle of obese insulin resistant mice, and knockout of Jnk1 (Jnk1−/−) leads to amelioration of insulin resistance in high fat diet
Adipose tissue from obese mice contains proportionately more M1 macrophages, whereas, lean adipose tissue contains more M2 macrophages, and increased M1 content positively correlates with inflammation, macrophage infiltration and insulin resistance
C-reactive protein (CRP)
these studies highlight the possibility that increased iNOS activity plays a direct role in the pathogenesis of insulin resistance
the important role of Ikkb in the development of obesity and inflammation-induced insulin resistance.
It is probable that local concentrations of inflammatory mediators, such as FFAs, Tnf or other cytokines/adipokines contribute to this polarity switch
Tnf and other cytokines/chemokines are symptomatic of inflammation, and while they propagate and/or maintain the inflammatory state, they are not the initial cause(s) of inflammation
Tlr4, in particular, is stimulated by lipopolysaccharide (LPS), an endotoxin released by gram-negative bacteria
Tlr4 belongs to the family of Toll-like receptors that function as pattern recognition receptors that guard against microorganismal infections as part of the innate immune system.
Tlr4 stimulation results in the activation of both Ikkb/NFκB and JNK/AP-1 signaling, culminating in the expression and secretion of pro-inflammatory cytokines/chemokines, including, Il1b, IL-6, Tnf, Mcp1, etc. (reviewed in [57
The fastest growing liver disease today is NAFLD, which is a direct result of the rising obesity epidemic. This is a good review of the current understanding on the pathophysiology of NAFLD.
Activation of inflammatory pathways in adipocytes impairs triglyceride storage and increases release of free fatty acids, an excess of which is known to induce insulin resistance in muscle and liver
recent studies have shown that large numbers of macrophages infiltrate obese adipose tissue,
It has been postulated that a paracrine loop involving free fatty acids and inflammatory cytokines establishes a vicious cycle between adipocytes and macrophages that propagates the inflammation
not only does interrupting the accumulation of macrophages within obese adipose tissue suppresses adipose inflammation in various animal models, it also ameliorates systemic insulin resistance and metabolic abnormalities, suggesting macrophages are key effector cells involved in adipose inflammation
Thus, obese visceral adipose tissue is clearly a site of chronic inflammation
activation of the leukocyte adhesion cascade, a hallmark of inflammation
CD8+ T cells within obese adipose tissue induce activation and migration of monocytes/macrophages, and in cooperation with the adipose tissue, they also induce macrophage differentiation. At the same time, obese adipose tissue activates CD8+ T cells, creating a vicious cycle involving CD8+ T cells, macrophages, and obese adipose tissue that propagates local inflammation
In obese adipose tissue there is a shift to dominance of CD8+ and TH1 T cells, which appears to propagate inflammation
Omeg-3, DHA and EPA, increased adiponectin production. In addition, blockade of the PPAR-gamma resulted in a reduction in adiponectin production. Thus PPAR gamma activation results in adiponectin production by adipocytes.
Meta-analysis finds no improvement with cardiovascular risk from low saturated fats. This is not the first study to show this. The weakness of this is that this study is a meta-analysis. This needs to be taken in context and applied individually. The take home is that universal restriction of saturated fats is not the holy grail of nutrition.
Numerous deletorious effects are seen in high fructose diets: elevated Triglyceride production, fatty liver, insulin resistance, increased VLDL production and secretion, increased deposit of TG in muscle and increased muscle insulin resistance. Alpha lipoic Acid is shown to counter these effects in rat model.
low EPA and DHA found in patients with Lupus. The authors of this article went so far as to say that lipid peroxides, NO, and anti-oxidants should be a part of the work up for patients with Lupus.
Palmitoleic acid and estimated D6D activity found to positively correlate with diabetes and worsening glucose control; In contrast, linoleum acid found to be inversely associated with glucose control and Diabetes development.
concussive brain injury
is a major cause of neuropsychological disability in spite of no obvious neuronal death
TBI elicits oxidative
damage to plasma membrane phospholipids
DHA is the most abundant polyunsaturated fatty acid (PUFA) in the brain,
where the DHA-containing phospholipids contribute to plasma membrane biogenesis and receptor signaling
curcumin has potent anti-inflammatory and antioxidant activities that can function to reduce
oxidative damage and cognitive deficits associated with neurological disorders
Curcumin provided in the diet before TBI can reduce oxidative damage and counteract TBI-related cognitive dysfunction
Our previous study indicated that n-3 fatty acids supplemented in the diet counteracted learning disability after TBI
curcumin contributes to enhance the effects of DHA on TBI by promoting phosphorylation of the
BDNF receptor TrkB in the hippocampus
previous evidence indicates that curcumin10 and DHA5 counteract TBI-related learning disability by involving BDNF
Our findings indicate
that curcumin counteracted the TBI-related reduction in n-3 DPA.
curcumin may promote the conversion of n-3 DPA to DHA
the combination of both nutrients has been reported to
produce anti-inflammatory action
the enhanced actions of curcumin and DHA in reducing cholesterol levels could be interpreted as preservation
of levels of phospholipids in the plasma membrane
curcumin and
DHA may contribute to reduce inflammation associated with the action of cholesterol in the pathology of TBI.
Curcumin and DHA shown to protect against TBI through a reduction in inflammation and maintenance of brain phospholipid membranes. BDNF is increases also.
strategies directed to preserve phospholipids in the plasma membrane such as the use of dietary docosahexaenoic
acid (C22:6n-3; DHA)5 can have beneficial effects for post-TBI recovery
DHA is the most abundant polyunsaturated fatty acid (PUFA) in the brain
The combination of curcumin and DHA had a trend of greater effects in
BDNF (117% of CTL; Figure 1C) compared with DHA or curcumin alone.
Our previous study indicated that n-3 fatty acids supplemented in the diet counteracted learning disability after TBI
There was a significant group effect on BDNF (F
4,25 = 5.229, P < .01 by ANOVA), and FPI reduced BDNF levels (50% of CTL, P < .01; Figure 1C), which was counteracted by DHA supplementation (90% of CTL, P < .05; Figure 1C). Curcumin also counteracted this reduction of BDNF
Curcumin provided in the diet before TBI can reduce oxidative damage and counteract TBI-related cognitive dysfunction.
curcumin contributed to enhance the action of DHA, protecting
against cognitive impairment, and these effects were associated with elevations in the BDNF receptor signaling
Our current results show that curcumin contributes to enhance the effects of DHA on TBI by promoting phosphorylation of the
BDNF receptor TrkB in the hippocampus.
previous evidence indicates that curcumin10 and DHA5 counteract TBI-related learning disability by involving BDNF
The effects of the DHA diet and curcumin on cognitive enhancement were consistent with enhanced elevations in BDNF receptor
signaling
effects of DHA and curcumin up to 2 weeks after TBI because this is the most critical period for the course of injury
recovery because the brain is metabolically dysfunctional during this time
What legacy do you leave your children? Study finds that the "lard legacy" is one many leave their children. Adults with high fatty acid profile, found in SAD, but this leaves alter gut microbiome in their children.
Effects of ethyl-eicosapentaenoic acid omega-3 fatty acid supplementation on hot flashes and quality of life among middle-aged women: a double-blind, placebo-controlled, randomized clinical trial.
Supplementation with E-EPA omega-3 fatty acid reduced HF frequency and improved the HF score relative to placebo