BNP and NT-proBNP associated with HF and worsening HF. Also, in the same setting, elevated BNP and NT-proBNP is found to be associated with increased cardiovascular events and mortality.
LPS leads to an increase in SOCS3 expression [20]. SOCS3 is a negative regulator of leptin signaling
We observed a significant increase in energy intake in the LPS-treated rats
the data provides a mechanism linking changes in gut microbiota induced by ingestion of HF diets to dysregulation of food intake and body weight
SOCS3 is an important mechanism by which leptin resistance develops in vagal afferent neurons and coincides with the onset of hyperphagia
Chronic low-dose LPS treatment induced TLR4 activation and MyD88 signaling in vagal afferent neurons, associated with increased SOCS3 expression and reduced leptin-signaling, characterized by the absence of leptin-induced pSTAT3.
We demonstrate that this chronic low dose LPS is sufficient to induce leptin–resistance in vagal afferent neurons, reduced sensitivity to the satiating effects of CCK, and loss of vagal afferent plasticity
it suggests that the increase in food intake and body weight we observed at week 6 in the LPS treated rats may be caused by LPS-induced leptin resistance.
chronic LPS treatment of mice for four weeks increased body weight
chronic LPS treatment of mice for four weeks increased subcutaneous fat
Very interesting study. High fat diet in rats induced gut flora change that resulted in LPS which induced appetite through leptin resistance and reduced cholecystokinin signaling.
Although currently no drugs that specifically target mitochondrial biogenesis in HF are available, acceleration of this process through adenosine monophosphate–activated kinase (AMPK), endothelial nitric oxide synthase (eNOS), and other pathways may represent a promising therapeutic approach
Mitochondrial biogenesis can be enhanced therapeutically with the use of adenosine monophosphate kinase (AMPK) agonists, stimulants of nitric oxide/cyclic guanosine monophosphate (NO/cGMP) pathway (including phosphodiesteraes type 5 inhibitors), or resveratrol
metformin, a commonly used antidiabetic drug that activates AMPK signaling
Recent evidence suggests that the eNOS/NO/cGMP pathway is an important activator of mitochondrial biogenesis
BH4 (tetrahydrobiopterin) supplementation can prevent eNOS uncoupling and was found to reduce left ventricular hypertrophy
folic acid is known to replenish reduced BH4 and has been shown to protect the heart through increased eNOS activity
Both folate deficiency and inhibition of BH4 synthesis were associated with reduced mitochondrial number and function
Resveratrol, a polyphenol compound responsible for the cardioprotective properties of red wine, was recently identified as a potent stimulator of mitochondrial biogenesis
epidemiological studies reveal a reduced risk of cardiovascular disease in premenopausal, but not post-menopausal, women compared with men
I would hypothesis that a change in the predominance of ER expression is one of ER beta to ER alpha: creating a more pro-inflammatory signal.
The majority of ROS in the heart appear to come from uncoupling of mitochondrial electron transport chain at the level of complexes I and III
Because the majority of ROS in HF comes from mitochondria, these organelles are the primary target of oxidative damage.
cardioprotective therapies such as angiotensin-converting enzyme inhibitors and ATII receptor blockers were shown to possess antioxidant properties, although it is not known whether they target mitochondrial ROS directly or indirectly
study finds no increased risk of CHD, HF, or CV death in subclinical hypothyroidism in older adults. No insight is gained from this article, due to the use of TSH as the only tool for thyroid assessment. TSH has been shown to become unreliable as a sole thyroid assessment tool an aging population.
Leptin, secreted by adipocytes in proportion to body fat mass
The saturated fatty acid palmitate (16:0) induces
NF-κB signaling through a TLR4-dependent mechanism
18:0 (stearic) and longer
saturated fatty acids as well as linolenic acid (18:3) increased proinflammatory cytokines, ER stress markers, and TLR4 activation
(SOCS)-3. A member of a protein family originally characterized as negative feedback regulators
of inflammation (13, 37), SOCS3 inhibits insulin and leptin signaling
IKKβ signaling in discrete neuronal subsets appears
to be required for both hypothalamic inflammation and excess weight gain to occur during HF feeding
the paradoxical observation that hyperphagia and weight gain occur when hypothalamic inflammation is induced
by HF feeding, yet when it occurs in response to systemic or local inflammatory processes (e.g. administration of endotoxin), anorexia and weight loss are the rule
, serves as a circulating signal of energy stores in part
by providing feedback inhibition of hypothalamic orexigenic pathways [e.g. neurons that express neuropeptide Y and agouti-related peptide (AgRP)]
and stimulating anorexigenic neurons
signals from Toll-like receptors (TLRs), evolutionarily conserved pattern recognition molecules critical for
detecting pathogens, amplified through signaling intermediates such as MyD88 activate the inhibitor of κB-kinase-β (IKKβ)/nuclear
factor-κB (NF-κB), c-Jun N-terminal kinase (Jnk) and other intracellular inflammatory signals in response to stimulation by
circulating saturated fatty acids
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
In this study, the cardioprotective effects of testosterone in testosterone-deprived rats heart with I/R injury were demonstrated
Prior to I/R injury, testosterone replacement provided cardioprotective effects in testosterone-deprived rats as indicated by (1) improved cardiac functions by markedly preserved %EF and %FS, and (2) attenuated cardiac sympathovagal imbalance by a markedly decreased LF/HF ratio
Testosterone replacement exerts cardioprotective effects by improving left ventricular function and cardiac sympathovagal balance impaired by testosterone deprivation in ORX rats
During the I/R period, testosterone replacement in ORX rats exerted the beneficial effects as indicated by (1) improved left ventricular pressure; (2) markedly decreased infarct size; (3) reduced fatal cardiac arrhythmias by increased time to 1st VT/VF onset and reduced arrhythmia scores; and (4) attenuated cardiac mitochondrial dysfunction caused by I/R injury by reducing ROS production, cardiac mitochondrial swelling and mitochondria membrane depolarization.
Chronic testosterone replacement also ameliorates left ventricular dysfunction, and reduces the infarct size and cardiac arrhythmias impaired by I/R injury under testosterone-deprived conditions
The mechanisms responsible for these beneficial effects of testosterone could be due to its ability to attenuate cardiac mitochondrial dysfunction and cardiomyocyte apoptosis
animal study finds that Testosterone therapy is cardioprotective in a preventative mode and with myocardial injury. Normalization of Testosterone in these animals with low T reduced infant injury size and improved heart function.
A good biomarker of intracardiac TH signaling would be helpful but has not been identified. In the absence of such a marker,
a rational, cautious therapeutic approach might be to restore and maintain over time biochemical euthyroidism as documented
by normal circulating levels of TSH, FT4, and FT3.
a low-T3 state resulting from altered peripheral TH metabolism secondary to caloric restriction is associated
with impaired cardiac contractility
Low-T3 syndrome is the central finding and defines the illness in a variety of acute and chronic severe nonthyroidal illnesses
with cardiac origin, including MI, HF, and surgically treated cardiac disease.1 Low circulating levels of T3 in the absence of primary thyroid hypofunction have been found in 20% to 30% of patients with
dilated cardiomyopathy.
Great review of the current understanding of thyroid hormone metabolism in cardiac tissue. Low T3 and increased rT3 (via increased D3 activity) is CLEARLY associated with poor cardiac performance and post MI and CHF is associated with poor outcomes. T3 is critical in cardiac remodeling and recovery post MI. T3 is actually a vasodilatory in the coronary arteries. Why a endocrinologist would call rT3 useless only points to their ignorance of the literature.
High fat diet in this small animal study finds an increase in reverse T3 and a decrease in T3. Higher carbohydrate diet provided no significant change.