Leptin Receptor Protein Analysis

Genetic research of obesity was partly successful in establishing obesity in model organisms – rodents where obesity occurs spontaneously together with other pathological aspects (insulin resistance, …). The main cause of monogenic obesity in these model organisms are common mutations always present in only one gene. Results of research on model organisms allowed us to understand biological mechanisms of calorie intake and regulation and maintenance of body weight. The most important insight into obesity was achieved in 1994 after discovery of ob gene encoding for leptin. In two years period, using screening method, candidate homologous genes, selected on genetic study basis on mice, another five genes were identified. Mutations on these genes were found to be the cause of autosomal recessive or dominant monogenic obesity. Products of these genes are leptin and its receptor, proopiomelanocortin (POMC) melanocortin receptor 4 (MC4R) and

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

“ 1. Adipokines are hormones produced by adipose tissue. /…/ Adipokines have effects not only on tissues but [also] on the hypothalamic and pancreatic function. /…/ 2. Elevated serum free fatty acids and high intracellular deposits of triglycerides and cholesterol. These lead to metabolic overload with interfere of insulin signaling and a decrease in tissue response to insulin. 3. Obesity causes release of inflammatory cytokines. /…/ These play an important role in the genesis of a fatty liver [which impairs the function]. 4.

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

And has been positively  correlated with visceral obesity and large prostrate tumors [4].  Studies have shown that leptin promotes the proliferation of androgen‐independent prostate  cancer cell lines. It has also been shown to promote vascular endothelial cell proliferation in vitro  and angiogenesis in vivo, processes that are crucial to allow cancer progression. Also, it has been  positively correlated with increased prostrate cancer cell migration (implying invasion and  metastasis) [5].  Mechanism of action ‐ The proliferative response of prostate cancer cells to leptin has been shown  to involve intracellular signalling molecules such as phosphatidyl‐inositol 3‐kinase (PI3‐K) and c‐Jun  NH2‐terminal kinase (JNK). [10]  o Interleukin‐6 – one third of the circulating level secretion of IL‐6 is from adipose tissue. It is directly  proportional to visceral obesity and insulin resistance. Its normal role being in modulation of  immune response and cell‐functions – it is basically a growth inhibitor. However, recently it has  been shown to undergo a transition in its role from growth inhibitor associated with  neuroendocrine differentiation to stimulator accompanied by androgen receptor activation in  prostrate cancer progression [6].  Prostrate cancer cultures have been shown to secrete high levels of IL‐6, and it is believed that  chronic exposure to this adipokine

Not just a simple hormone, but a very strong one. This hormone basically tells your brain how much fat you have, what to do with it, and also - where to store it. It really tells the brain what to do. That’s why leptin controls appetite, fat-loss, and decides whether you have fat in your belly, hips, or spread evenly all over your

The broken down food contains nutrients that activates the G-protein coupled receptors of enteroendocrine cells (Sam et al, 2012). On activation, it releases a number of gut hormones which passes the nutrient availability signal to the hypothalamic arcuate nucleus (ARC). This ARC is known to mediate intake of food and energy expenditure. (Peruzzo et al, 2000; Schaeffer et al, 2014; Sainsbury et al, 2010). Several circulating peptides: insulin and leptin are responsible for adiposity and energy deposits. ARC has two neural populations that act antagonist to each other. The medial part contains orexigenic neurons that regulate neuropeptide Y (NPY) and agouti-related protein (AgRP). The lateral part acts as an anorexigenic neurons expressing alpha-melanocyte-stimulating hormone (a-MSH) formed from pro-opiomelanocortin (POMC) and cocaine-amphetamine regulated transcript (CART) (Hahn et al, 1998; Elias et al,

Melanocortin-4 receptor (MC4R) is a G protein–coupled receptor expressed in the brain’s hypothalamus where it regulates energy homeostasis. MC4R agonists function to lower food intake and weight. In this respect, while obesity promotes hyperlipidemia and hypothalamic injury, MC4R agonists are nevertheless more effective to reduce food intake within hours of administration in overweight, rather than lean, mice. MC4R undergoes constitutive internalization and recycling to the plasma membrane, with agonist binding inducing receptor retention along the intracellular route and, under prolonged exposure, desensitization. Here, we found that, in neuronal cells, lipid stress by exposure to elevated palmitate leaves unchanged the rate

CB presents as an overweight, but by BMI standards she is obese. Obesity is a risk factor for many health concerns including diabetes because of insulin resistance. There are several reasons as to how resistance occurs with obesity (McCance & Huether, 2014). First, adipokines which are hormones that are produced by adipose, or fat tissue are present (McCance & Huether, 2014). These hormones are responsible for increasing the levels of leptin, and decreasing the adiponectin (McCance & Huether, 2014). According to Helen Dodson, the hormone leptin is acts to control metabolism, appetite, and body weight (2014). If the levels are increased, causing leptin resistance, then the patient may feel hunger that is not really there but the body "needs" more glucose for fuel. Leptin resistance makes it difficult for the insulin to be used properly, causing the body to not obtain the necessary nutrients for energy and metabolism (Diseases and conditions, 2016).

Fat is important in the dietary needs of a human and can provide energy as well. Fats also play a vital role in maintaining body temperature, insulating organ from shock, and much more. Although fat seems to have many benefits it can also take a toll in the human body. White fat stores calories and is the major source for energy but an excess of white fat can lead to complications. For example, white fat is associated with sleep apnea and other physical disabilities such as knee arthritis. White fat produces a form of estrogen and leptin, a hormone that helps regulate appetite and hunger; it also consists of receptors for growth hormone, insulin, adrenaline, and cortisol, a stress hormone. The consumption of too many calories and expending of too few calories causes white fat. On the other hand, brown fat cells burn energy and produce heat. Although for some it may be more than for others everyone has brown fat, individuals with lower body mass index (BMI) can have more brown fat. Looking at it through a developmental aspect, as an individual passes infancy the amount of this type of fat can decrease. Brown fat is activated by cold and can be even grown, along with exercise, and is being currently studied as a way to help individuals struggling with

hormone that plays a major role in the creation of fat cells in the body.

The catecholamines consist of norepinephrine and epinephrine, and their role is activate B-adrenergic receptors (βARs) to increase cAMP levels and cAMP-dependent protein kinase A (PKA) activity. This phosphorylation stimulates the release of adipose energy stores due to lipolysis (the hydrolysis of triglycerides) and the liberation of free fatty acids. Insulin is the opposing metabolic regulator that antagonizes the action of catecholamines to stimulate lipolysis by activating phosphodiesterases that degrade cAMP and by using the protein kinase AKT to activate lipid synthesis pathways to promote energy

After leptin is secreted by the adipose tissue, it enters the brain through the bloodstream. Gastric leptin may also reach hypothalamus through the vagal nerve and nucleus solitarius. Effects of leptin on various systems have been reported, including reproduction, immune system, hematopoesis, angiogenesis, bone formation and wound healing. It plays an important role in energy balance by inhibiting energy intake contrary to ghrelin, and by regulating body weight and energy homeostasis (Moran & Phillip, 2003).

Rankenin et al. dected over 300 genes and gene markers that have a central role in the etiology of obesity but , the specifics on which genes promote obesity and which genes are protective against obesity is unknown .However, some single-gene defects have been discovered in animals and confirmed in humans through congenital leptin deficiencies, which can lead to hyperphagia and the development of obesity. Although there are confirmed single-gene defects

This system is comprised of POMC and AgRP neurons of the arcuate hypothalamus (Arc), neuropeptides alpha-MSH and AgRP, and central melanocortin receptors (MCRs) MC3R and MC4R. POMC and AgRP neurons monitor energy state and change their activity to alter feeding and body weight. During positive energy state, POMC neurons release α-MSH which acts as an agonist on MC3R and MC4R. AgRP is released during negative energy state and is a reverse agonist/antagonist of the central MCRs. Stimulation of POMC neurons or injection of α-MSH or MTII, MC3R/MC4R agonist, decreases food intake and body weight (Fan et al., 1997, Pierroz et al., 2002, Aponte et al., 2011). AgRP neuron activation, central administration or overexpression of AgRP stimulates food intake and weight gain (Graham et al., 1997, Ollmann et al., 1997, Rossi et al., 1998, Aponte et al., 2011, Krashes et al., 2011). Knockout of MC3R or MC4R results in increased weight and fat mass, diabetes, and altered activity (Huszar et al., 1997, Butler et al., 2000, Chen et al., 2000) suggesting that both receptor subtypes are important for energy homeostasis. Majority of research indicates a primary role for MC4Rs in the actions of α-MSH and AgRP while the role of MC3R is less understood (Harrold et al., 1999). Nevertheless, MC3R may be an important contributor to energy homeostasis as central administration