Prohibitin Inactivation in Adipocytes Results in Reduced Lipid Metabolism and Adaptive Thermogenesis Impairment

Prohibitin-1 (PHB) is a multifunctional protein previously reported to be important for adipocyte function. PHB is expressed on the surface of adipose cells, where it interacts with a long chain fatty acid (LCFA) transporter. Here, we show that mice lacking PHB in adipocytes (PHB Ad-KO) have a defect in fat tissue accumulation despite having larger lipid droplets in adipocytes due to reduced lipolysis. Although PHB Ad-KO mice do not display glucose intolerance, they are insulin resistant. We show that PHB Ad-KO mice are lipid intolerant due to a decreased capacity of adipocytes for LCFA uptake. Instead, PHB Ad-KO mice have increased expression of glucose transporter GLUT1 in various tissues and use glucose as a preferred energy source. We demonstrate that PHB Ad-KO mice have defective brown AT, are cold-intolerant, and display a reduced basal energy expenditure. Systemic repercussions of PHB inactivation in adipocytes were observed in both males and females. Consistent with lower cellular mitochondrial content and reduced UCP1 protein expression, brown adipocytes lacking PHB display decreased proton leak and switch from aerobic metabolism to glycolysis. Treatment of differentiating brown adipocytes with small molecules targeting PHB suppressed mitochondrial respiration and uncoupling. Our results demonstrate that PHB in adipocytes is essential for normal fatty acid uptake, oxidative metabolism, and adaptive thermogenesis. We conclude that PHB inhibition could be investigated as an approach to altering energy substrate utilization.

Prohibitin Inactivation in Adipocytes Results in Reduced Lipid Metabolism and Adaptive Thermogenesis Impairment

Prohibitin-1 (PHB) is a multifunctional protein previously reported to be important for adipocyte function. PHB is expressed on the surface of adipose cells, where it interacts with a long chain fatty acid (LCFA) transporter. Here, we show that mice lacking PHB in adipocytes (PHB Ad-KO) have a defect in fat tissue accumulation despite having larger lipid droplets in adipocytes due to reduced lipolysis. Although PHB Ad-KO mice do not display glucose intolerance, they are insulin resistant. We show that PHB Ad-KO mice are lipid intolerant due to a decreased capacity of adipocytes for LCFA uptake. Instead, PHB Ad-KO mice have increased expression of glucose transporter GLUT1 in various tissues and use glucose as a preferred energy source. We demonstrate that PHB Ad-KO mice have defective brown AT, are cold-intolerant, and display a reduced basal energy expenditure. Systemic repercussions of PHB inactivation in adipocytes were observed in both males and females. Consistent with lower cellular mitochondrial content and reduced UCP1 protein expression, brown adipocytes lacking PHB display decreased proton leak and switch from aerobic metabolism to glycolysis. Treatment of differentiating brown adipocytes with small molecules targeting PHB suppressed mitochondrial respiration and uncoupling. Our results demonstrate that PHB in adipocytes is essential for normal fatty acid uptake, oxidative metabolism, and adaptive thermogenesis. We conclude that PHB inhibition could be investigated as an approach to altering energy substrate utilization.

Thyroid Function and Obesity: From Mechanisms to the Benefits of Levothyroxine in Obese Patient

Background: Thyroid disease and obesity are very common clinical conditions in the general population. They can occur together in the same subject, but their relationship does not seem to be exclusively stochastic. Aim: We critically reviewed the evidence of the literature in the attempt to provide explanation for this association, in order to understand the possible benefits of levothyroxine therapy in euthyroid obese patients. Results: A low energy expenditure rate can lead to obesity. Maintaining Basal Metabolic Rate (BMR) is the main cause of energy expenditure for the body, which is regulated by thermogenesis. Thyroid hormone receptors (TR) play different roles in the induction of thermogenetic mechanisms: TRα is fundamental to induce thermogenesis, TRβ triggers the expression of uncoupling protein 1(UCP1). Despite such mechanisms, there is not currently evidence to treat subjects suffering from obesity with thyroid hormones. Conclusion: Replacement therapy should be reserved to patients with obvious signs of subclinical or clinical hypothyroidism. Definitions: Basal metabolic rate (BMR) or basal energy expenditure (BEE): measurement obtained under total inactivity and controlled research conditions; resting energy expenditure (REE): measurement obtained when an individual is sitting quietly (is mildly higher than BMR/BEE).

Post-Exercise Ketosis, Salivary Uric Acid and Interleukin-6 after a Simulated Wheelchair Basketball Match

Background:: Interleukin (IL)-6, total antioxidant capacity (TAC) and uric acid (UA) increase after exercise in able-bodied individuals. Wheelchair Basketball Athletes (WBA), having low muscle mass, could be at risk of post-exercise ketosis. Objective:: This study aimed to evaluate the post-exercise ketosis, IL-6 and antioxidant response, in WBA of the Italian National team, after a simulated match. Methods:: Dietary intakes, Starvation Symptoms Inventory (SSI), percentage of fat mass (FM%) and basal Respiratory Exchange Ratio (RER) and Basal Energy Expenditure (BEE), were evaluated. Salivary TAC, UA and IL-6 were measured: before (PreM), at the end (EM) and 20 minutes after (PostM) the match. Capillary glucose and β-hydroxybutyrate (βHB) were monitored. Percentage of Heart Rate Reserve (%HRR) was measured to evaluate exercise intensity. Results:: WBA had low carbohydrates (43.5% of daily energy intake (En)) and high fat (36.3% En) intakes. The increase in UA at PostM correlated with En (0.810, p<0.01) and was inversely related to βHB at EM (-0.719, p<0.05). Furthermore, at PostM growing IL-6 levels correlated with BEE (0.778, p<0.05) and inversely related to FM% (-0.762, p<0.5) were found, which in turn was correlated to SSI (0.781, p<0.05). Also βHB PostM correlated with SSI (0.761, p<0.05) but was inversely related to RER (-0.745, p<.05) and En (-0.826, p<0.01). Conclusions:: Our study suggests that some WBA should improve their dietary habit in order to prevent post-exercise ketosis and ameliorate the endogenous antioxidant response after exercise.

Cardiolipin content controls mitochondrial coupling and energetic efficiency in muscle

Unbalanced energy partitioning participates in the rise of obesity, a major public health concern in many countries. Increasing basal energy expenditure has been proposed as a strategy to fight obesity yet raises efficiency and safety concerns. Here, we show that mice deficient for a muscle-specific enzyme of very-long-chain fatty acid synthesis display increased basal energy expenditure and protection against high-fat diet–induced obesity. Mechanistically, muscle-specific modulation of the very-long-chain fatty acid pathway was associated with a reduced content of the inner mitochondrial membrane phospholipid cardiolipin and a blunted coupling efficiency between the respiratory chain and adenosine 5′-triphosphate (ATP) synthase, which was restored by cardiolipin enrichment. Our study reveals that selective increase of lipid oxidative capacities in skeletal muscle, through the cardiolipin-dependent lowering of mitochondrial ATP production, provides an effective option against obesity at the whole-body level.

DYSLIPIDEMIA IN THYROID DISORDERS

Background: Thyroid hormones influence nearly all major metabolic pathways. Their most obvious and well-known action is the increase in basal energy expenditure obtained by acting on protein, carbohydrate and lipid metabolism. The lipid metabolism is more influenced by the thyroid hormone. Methods: A cross-sectional study was conducted on 100 patients with suspicion of thyroid disorders were taken as cases. One hundred patients with normal thyroid profile and no history of other chronic diseases were taken as control group. Results: The serum TC, TG and LDL levels in hypothyroid individuals (both overt and subclinical) were significantly higher than euthyroid subjects but the levels were comparable between hyperthyroid and euthyroid group. Conclusion: Dyslipidemias are associated with thyroid disorders, so biochemical screening for thyroid dysfunction in all dyslipidemic patients. Therefore, patients presenting with dyslipidemia are recommended for investigation to explore thyroid dysfunction. Keywords: Thyroid profile, Total cholesterol, Triglycerides and LDL