Leptin Resistance Research Paper

In wild type mouse there is no effect on food intake, body weight and blood glucose though we give more leptin because here the leptin receptors are constant. But, in ob/ob mouse the food intake, body weight and blood glucose levels are decrease because the presence of leptin receptor. However, in the db/db mouse there is no effect due to the absence of the leptin

For example leptin deficiency, leptin is just a hormone that controls weight by telling your brain to consume less food

The body must keep a healthy blood glucose level so that there is a continuous supply of energy to the cells. If the blood sugar levels fall too low (hypoglycaemia) it can cause harmful complications such as fatigue and even loss of consciousness. If blood sugar levels raise too high (hyperglycaemia) it can lead to many difficulties such as cardiovascular disease, nerve damage and kidney damage (S Preet, 2013). This is why is important for the body to regulate its glucose levels. It does this by the pancreatic islets detecting a change in blood glucose levels, they then release the hormone insulin into the blood stream. Muscle cells are prompted by the insulin, to absorb glucose. The way insulin does this is by binding itself to receptors on the cell membrane, thuds increasing the amount of transporters and allowing more glucose to be transported into the cells. If glucose levels fall then another hormone is released by the pancreas called glucagon. Glucagon allows stored glucose (glycogen) to be released from the liver into the blood stream and raises blood glucose levels (Amis, 2011). This process of keeping blood glucose levels constant is an example of ‘homoeostatic control’ where the rise and fall of glucose levels allows each different hormone to be used in a constant

Strosberg, A. D. and Issad, T. The involvement of leptin in humans revealed by mutations in leptin and leptin receptor genes. Trends Pharmacol. Sci. 6(1), 227-230

1994). Leptin is secreted primarily by adipocytes, proportionally to fat cell mass, and contributes to energy metabolism. Leptin will affect the energy balance by acting on the brain. Leptin can activate, directly or indirectly, specific centers in the hypothalamus to decrease food intake, to increase any energy expenditure, to influence the glucose, lipid metabolism, and alter neuroendocrine function (Campfield, Smith et al. 1995). Leptin resistance, in regards to obesity, was coined due to the increased leptin levels with no impact on regulating energy homeostasis. Leptin resistance causes insulin resistance and the accumulation of lipids is a direct result of the reduction of lipid oxidation in insulin-sensitive organs; shown in preclinical and clinical experiments with obese rodents and humans. However, the mechanisms that may lead to leptin resistance are still being researched (Mori, Hanada et al.

In the hope that Lepin would solve this epidemic, leptin has attracted much attention as being the most important peripheral signals for the maintenance of energy homeostasis (Ahima, 2008). For example, a study approved by the Cambridge Local Research Ethics Committee in Cambridge, discovered that a nine year old girl with extreme obesity was found to have leptin deficiency. Leptin therapy allowed her to reduce her weight to the normal range. In summary, the effects of leptin therapy within the child who had a leptin deficiency, confirmed the importance of leptin in the regulation of body weight in humans and the role for

Over two thirds of US adults are overweight or obese22 generating an estimated health care cost of $150 billion2. Obesity is one of the major risk factors for development of type 2 diabetes, cardiovascular disease, and cancer23. Energy homeostasis relies on an intricate balance between energy intake and expenditure and disruption in this balance can result in obesity. Feeding is a complex behavior and is largely regulated by two systems. Feeding to maintain metabolic needs, or homeostatic feeding, is regulated by homeostatic feeding circuits, whereas reward-based intake of palatable food, such as foods rich in fat and sugar, is regulated by the mesolimbic DA system23,24. The two systems are not autonomous, however. Energy deficit

Incretins, are gut-derived hormones released predominantly by the L cells in the distal bowel in response to a meal. They reduce blood sugar concentrations by enhancing the insulin release from pancreatic beta cells and inhibiting postprandial glucagon secretion and gastric emptying after a meal (Hattori). Ghrelin, a peptide produced by the stomach, stimulates appetite and its levels increase with fasting and decrease after a meal (Cummings). It also has a pro-diabetic role, causing hyperglycemia through inhibition of insulin resistance and stimulation of release of counter-regulatory hormones, and impairing insulin sensitivity (Leite-Moreira). A peptide Obestatin, derived from ghrelin precursor but with opposite effects has recently been found to be produced by the same neuroendocrine cells that secrete the orexigenic hormone but counterbalances its effects by decreasing appetite (Zhang).

Illustrated model of adipokine-endothelial cell interaction. Adipocytes generates many hormones and cytokines such as TNF-α, PAI-1, leptin, adiponectin, and resistin. These factors have a main role in adipose tissue, and act locally. They also are important in cell signaling, and have significant effects as circulating bioactive factors. Resistin directly stimulates the activation of endothelial and modulates endothelial function, so this represents resistin is an important link between insulin resistance and cardiovascular

To look at the involvement of canonical insulin/PI3K/Akt pathway in adipocytes leptin secretion the study measured it using insulin resistant DIO mice with HFD and CD fed mice, with the HFD mice gaining higher body and fat mass. Cell lysate of both HFD and CD fed mice were subjected to western blotting and it was observed that phospho-Akt level in adipocytes from HFD fed mice was lower than the CD fed mice after insulin stimulation, showing insulin resistance in the HFD fed mice. Also, the fasting leptin level of HFD fed mice is ten times higher than the CD fed mice. Refeeding, resulted in no significant increase in plasma leptin levels in HFD fed mice after two hours, whereas with the CD fed mice there was a significant increase in plasma leptin levels. This implies that leptin production and/or secretion after refeeding is impaired in HFD fed mice. To verify that there is a decrease in systematic leptin level, the researchers isolated primary adipocytes from HFD and CD fed mice and then determined ISLS in ex vivo. The result was that ISLS was significantly lower in primary adipocytes from HFD fed mice. This supports the hypothesis that impaired ISLS in HFD fed mice in vivo and ex vivo was dependent on PI3K/Akt activation. Furthermore, there is an essential role of PI3K/Akt in regulating ISLS in primary adipocytes as seen when blocking PI3K activity with wortmannin. This significantly inhibits ISLS without affecting basal leptin secretion. Also, AKT 1/2 inhibitor Akti

The biochemistry of metabolic syndrome breaks down to the signal of the leptin gene (tells the brain to produce energy) becomes blocked by insulin from reaching the hypothalamus, which causes an individual to always feel hungry, instead of burning off the energy. Subsequently, a few variables trigger the process; a small percentage

Insulin is a peptide hormone produced by beta cells in the pancreas, and by Brockmann body in some teleost fish. It regulates the metabolism of carbohydrates and fats by promoting the absorption of glucose from the blood to skeletal muscles and fat tissue and by causing fat to be stored rather than used for energy. Insulin also inhibits the production of glucose by the liver.

Because visceral adipocytes have more glucocorticoid receptors than subcutaneous adipose cells, such an activated hypothalamic-pituitary-adrenal axis may promote preferential fat deposition in the visceral adipose depot while at the same time inducing insulin resistance in the liver and in the skeletal muscle.74

The neuronal loss impairs insulin and leptin signaling and impacts energy balance as well as pituitary and adrenal activity. In contrast to other models of obesity, MSG-treated rats are characterized by hyperinsulinemia, normoglycemia, elevated basal corticosterone level as well as increased lipogenesis and reduced lipolysis in the adipose tissue, despite their normophagia. Besides, MSG-treated rats show unchanged or decreased body weight in comparison to control

Based on mammalian studies, NPY stimulates adipocyte proliferation and differentiation [6]. Our group also reported that NPY promotes adipogenesis during the early and later stages of chicken preadipocyte differentiation [9, 15]. NPY exerts its functions by binding to a variety of NPY receptors (NPYRs), with the most well-known ones associated with appetite and adipose physiology being NPYR1, NPYR2 and