Insulin resistance (IR) is considered as a pathological condition in which cells fail to respond normally to the hormone insulin. To prevent hyperglycemia and noticeable organ damage over time, the body produces insulin when glucose starts to be released into the bloodstream, primarily from the digestion of carbohydrates in the diet. Under normal conditions of insulin reactivity, this insulin response triggers glucose being taken into body cells, to be used for energy, and inhibits the body from using fat for energy, thereby causing the concentration of glucose in the blood to decrease as a result, staying within the normal range even when a large amount of carbohydrates is consumed. Carbohydrates comprise simple sugars, i.e. monosaccharides, such as glucose and fructose, disaccharides, such as cane sugar, and polysaccharides, e.g. starches. Fructose, which is metabolised into triglycerides in the liver, stimulates insulin production through another mechanism, and can have a more potent effect than other carbohydrates. A habitually high intake of carbohydrates, and particularly fructose, e.g. with sweetened beverages, contributes to insulin resistance and has been linked to weight gain and obesity. If excess blood sugar is not sufficiently absorbed by cells even in the presence of insulin, the increase in the level of blood sugar can result in the classic hyperglycemic triad of polyphagia, polydipsia, and polyuria. Avoiding carbohydrates and sugars, a no-carbohydrate diet or fasting can reverse insulin resistance.
Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is synthesized in the pituitary from the 285-amino-acid-long polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 44-amino-acid-long signal peptide sequence during translation.
Leptin is a hormone predominantly made by adipose cells that helps to regulate energy balance by inhibiting hunger. This hormone acts on receptors in the arcuate nucleus of the hypothalamus. In obesity, a decreased sensitivity to leptin occurs, resulting in an inability to detect satiety despite high energy stores and high levels of leptin.
Appetite is the desire to eat food, sometimes due to hunger. Appealing foods can stimulate appetite even when hunger is absent, although appetite can be greatly reduced by satiety. Appetite exists in all higher life-forms, and serves to regulate adequate energy intake to maintain metabolic needs. It is regulated by a close interplay between the digestive tract, adipose tissue and the brain. Appetite has a relationship with every individual's behavior. Appetitive behaviour also known as approach behaviour, and consummatory behaviours, are the only processes that involve energy intake, whereas all other behaviours affect the release of energy. When stressed, appetite levels may increase and result in an increase of food intake. Decreased desire to eat is termed anorexia, while polyphagia is increased eating. Dysregulation of appetite contributes to anorexia nervosa, bulimia nervosa, cachexia, overeating, and binge eating disorder.
Orexin, also known as hypocretin, is a neuropeptide that regulates arousal, wakefulness, and appetite. The most common form of narcolepsy, in which the sufferer experiences brief losses of muscle tone (cataplexy), is caused by a lack of orexin in the brain due to destruction of the cells that produce it.
In biology, adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular endothelial cells and a variety of immune cells such as adipose tissue macrophages. Adipose tissue is derived from preadipocytes. Its main role is to store energy in the form of lipids, although it also cushions and insulates the body. Far from being hormonally inert, adipose tissue has, in recent years, been recognized as a major endocrine organ, as it produces hormones such as leptin, estrogen, resistin, and the cytokine TNFα. The two types of adipose tissue are white adipose tissue (WAT), which stores energy, and brown adipose tissue (BAT), which generates body heat. The formation of adipose tissue appears to be controlled in part by the adipose gene. Adipose tissue – more specifically brown adipose tissue – was first identified by the Swiss naturalist Conrad Gessner in 1551.
Adiponectin is a protein hormone which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ADIPOQ gene and it is produced in adipose tissue.
Ghrelin, the "hunger hormone", also known as lenomorelin (INN), is a peptide hormone produced by ghrelinergic cells in the gastrointestinal tract that functions as a neuropeptide in the central nervous system. Besides regulating appetite, ghrelin also plays a significant role in regulating energy homeostasis.
Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized only in neuropeptide Y (NPY)-containing cell bodies located in the ventromedial part of the arcuate nucleus in the hypothalamus. AgRP is co-expressed with NPY and acts to increase appetite and decrease metabolism and energy expenditure. It is one of the most potent and long-lasting of appetite stimulators. In humans, the agouti-related peptide is encoded by the AGRP gene.
Neuroendocrinology is the branch of biology which studies the interaction between the nervous system and the endocrine system, that is how the brain regulates the hormonal activity in the body. The nervous and endocrine systems often act together in a process called neuroendocrine integration, to regulate the physiological processes of the human body. Neuroendocrinology arose from the recognition that the brain, especially the hypothalamus, controls secretion of pituitary gland hormones, and has subsequently expanded to investigate numerous interconnections of the endocrine and nervous systems.
A branched-chain amino acid (BCAA) is an amino acid having an aliphatic side-chain with a branch. Among the proteinogenic amino acids, there are three BCAAs: leucine, isoleucine, and valine. Non-proteinogenic BCAAs include 2-aminoisobutyric acid.
Fat mass and obesity-associated protein also known as alpha-ketoglutarate-dependent dioxygenase FTO is an enzyme that in humans is encoded by the FTO gene located on chromosome 16. As one homolog in the AlkB family proteins, it is the first mRNA demethylase that has been identified. Certain variants of the FTO gene appear to be correlated with obesity in humans.
Leptin receptor also known as LEP-R or OB-R is a Type I cytokine receptor, a protein that in humans is encoded by the LEPR gene. LEP-R functions as a receptor for the fat cell-specific hormone leptin. LEP-R has also been designated as CD295. Its location is the cell membrane, and it has extracellular, trans-membrane, and intracellular sections.
Adipose tissue is an endocrine organ that secretes numerous protein hormones, including leptin, adiponectin, and resistin. These hormones generally influence energy metabolism, which is of great interest to the understanding and treatment of type 2 diabetes and obesity.
Achim Peters, Prof. Dr. is a German obesity specialist who lives and works in Lübeck. He developed the "Selfish Brain" theory and since 2004 has been leading the clinical research group supported by the German Research Foundation (DFG) “Selfish Brain: Brain glucose and Metabolic syndrome".
In biology, energy homeostasis, or the homeostatic control of energy balance, is a biological process that involves the coordinated homeostatic regulation of food intake and energy expenditure. The human brain, particularly the hypothalamus, plays a central role in regulating energy homeostasis and generating the sense of hunger by integrating a number of biochemical signals that transmit information about energy balance. Fifty percent of the energy from glucose metabolism is immediately converted to heat.
Jeffrey Scott Flier is an American physician, endocrinologist, researcher, and the 21st Dean of the Faculty of Medicine at Harvard University.
Christos Socrates Mantzoros is a Greek American physician scientist, internist - endocrinologist, researcher, Harvard Medical School professor and the editor-in-chief of the journal Metabolism: Clinical and Experimental. He is considered a pioneer and worldwide expert in obesity and metabolism. He has given more than 500 lectures nationally and internationally on these critical topics. His research has resulted in more than 800 publications in Medline, including more than 150 publications under the collaborative Look Ahead Research Group, more than 200 chapters and reviews and has received more than 72,000 citations with an h-index=121 as well as prestigious awards at national and international meetings. He has an H index of 114.
There are many possible pathophysiological mechanisms involved in the development and maintenance of obesity. This field of research had been almost unapproached until the leptin gene was discovered in 1994 by J. M. Friedman's laboratory. These investigators postulated that leptin was a satiety factor. In the ob/ob mouse, mutations in the leptin gene resulted in the obese phenotype opening the possibility of leptin therapy for human obesity. However, soon thereafter J. F. Caro's laboratory could not detect any mutations in the leptin gene in humans with obesity. On the contrary Leptin expression was increased proposing the possibility of Leptin-resistance in human obesity. Since this discovery, many other hormonal mechanisms have been elucidated that participate in the regulation of appetite and food intake, storage patterns of adipose tissue, and development of insulin resistance. Since leptin's discovery, ghrelin, insulin, orexin, PYY 3-36, cholecystokinin, adiponectin, as well as many other mediators have been studied. The adipokines are mediators produced by adipose tissue; their action is thought to modify many obesity-related diseases.
Fetal programming, also known as prenatal programming, is a theory which suggests that the environment surrounding the fetus during its developmental phase, plays a seminal role in determining its disease risk during the later stages.
