Leptin and Adiponectin in Obesity PDF

Leptin & adiponectin in obesity Leptin The hormone leptin (from the Greek word ''leptos'' meaning ''thin'') is a 167-amino acid peptide hormone encoded by theob (obesity) gene and secreted by white adipocytes. Its discovery, has greatly improved our understanding of how the adipose tissue "communi...

Leptin & adiponectin in obesity Leptin The hormone leptin (from the Greek word ''leptos'' meaning ''thin'') is a 167-amino acid peptide hormone encoded by theob (obesity) gene and secreted by white adipocytes. Its discovery, has greatly improved our understanding of how the adipose tissue "communicates" with other systems in the body, in particular with the central nervous system (CNS). Following release into the circulation, leptin crosses the blood–brain barrier and binds to presynaptic GABAergic neurons of the hypothalamus of the central nervous system (CNS) to control appetite and energy expenditure. One of leptin’s more important roles is thought to be as a signal of inadequate food intake or starvation. For example, leptin levels decline during fasting, low-calorie dieting, or uncontrolled type 1 diabetes. In these situations,the reduced leptin levels stimulate hunger while decreasing energy expenditure and engendering other physiologicadaptations that restore fat stores to baseline. On the other hand, serum concentrations of leptin increase in proportion to increasing adiposity. As a regulatory signalin a homeostatic system, higher circulating levels of leptin should result in decreased energy intake and elevated energy expenditure, but this is not the case when individuals become overweight or obese, suggesting a state of leptin resistance. Obesity is associated with decreasing levels of circulating soluble leptin receptors (SLR). These receptors are proteins that circulate in the blood and contribute directly to leptin function. This state of high leptin levels andlow SLR may explain in part why obese individuals are resistant to leptin. Decreased transport across the blood brain barrier and also a decreased ability of leptin to activate hypothalamic signaling in diet-induced obesity may be crucial mediators in the pathogenesis of leptin resistance that leads to failure to adequately compensate forthe positive energy balance leading to unwanted weight gain and obesity. This postulated leptin resistance is a majortarget in the search for a better understanding of obesity and the development of pharmacological tools to treat this chronic disease. Leptin not only links fat tissue with the CNS, but also to other tissues in the body. Leptin receptors are present inperipheral organs, such as the liver, skeletal muscles, pancreatic beta cells, and even adipose cells, indicating endocrine,autocrine, and paracrine roles of leptin in energy regulation. Leptin signaling in these organs is thought to mediateimportant metabolic effects. Leptin has been implicated in glucose and lipid metabolism as an insulin-sensitizer. It has been shown to decrease glucagon synthesis and secretion, decrease hepatic glucose production and increase insulin hepatic extraction, decrease lipogenesis in the adipose tissue and increase lipolysis among multiple other beneficial effects on insulin and lipids metabolism (18). Leptin receptors are present in pancreatic β-cells, and leptin inhibits insulin biosynthesis and secretion from pancreatic β-cells. By contrast, insulin stimulates leptin secretion from adipose tissue. This hormonal regulatory feedback loop is an important adipo-insular axis. Dysfunction of this adipo-insular crosstalk plays an important role in the development of hyperinsulinemia and type 2 diabetes mellitus. If leptin is delivered directly into the brain, it reduces feeding, but delivery into the blood is essentially without effect. Adiponectin Adiponectin is another important adipocytokine that influences insulin sensitivity and atherogenesis. Adiponectin mediates its effect through binding to receptors AdipoR1 and AdipoR2, leading to activation of adenosine monophosphate dependent kinase, PPAR-α, and other yet-unidentified signaling pathways. Lower levels ofadiponectin in obesity have been associated with insulin resistance, dyslipidemia, and atherosclerosis in humans. With weight loss, plasma adiponectin levels significantly increase in parallel with improvements in insulin sensitivity. Adiponectin also suppresses the action of inflammatory cytokines such as tumor necrosis factor alpha (TNF-alpha), favorably modulates natural killer cell function and other immune regulatory molecules, and improves dyslipidemia and other risk factors of cardiovascular disease. In addition to an anti-atherogenic effect, adiponectin may also have a variety of anti-tumor effects. This effect ofadiponectin is thought to be mediated, in part, through inhibition of leptin induced tumor proliferation (31). It retards theaggressiveness of tumors and their metastatic potential of tumors and hypoadiponectinemia have been associated with aseveral cancers including breast, gastric, lung, prostate and others. The primary mechanisms by which adiponectin enhance insulin sensitivity appears to be through increased fatty acid oxidation (in skeletal muscle) and inhibition of hepatic glucose production. References:  doi: 10.3389/fnins.2013.00051  PMID: 25905281  DOI: 10.1111/j.1467-789X.2005.00159.x