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Pathophysiology Of Obesity
Pathophysiology of obesity is the study of disordered physiological processes that cause, result from, or are otherwise associated with obesity. A number of possible pathophysiological mechanisms have been identified which may contribute in the development and maintenance of obesity. Obesity results from a complex interplay of genetic, hormonal, neural, and environmental factors that dysregulate energy balance. Research 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 ob ...
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Leptin
Leptin (from Ancient Greek, Greek λεπτός ''leptos'', "thin" or "light" or "small"), also known as obese protein, is a protein hormone predominantly made by adipocytes (cells of adipose tissue). Its primary role is likely to regulate long-term Energy homeostasis, energy balance. As one of the major signals of energy status, leptin levels influence appetite, Hunger (physiology), satiety, and motivated behaviors oriented toward the maintenance of energy reserves (e.g., feeding, foraging behaviors). The amount of circulating leptin correlates with the amount of energy reserves, mainly Triglyceride, triglycerides stored in adipose tissue. High leptin levels are interpreted by the brain that energy reserves are high, whereas low leptin levels indicate that energy reserves are low, in the process adapting the organism to Starvation response, starvation through a variety of metabolic, endocrine, neurobiochemical, and behavioral changes. Leptin is coded for by the ''LEP'' gene ...
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Duodenum
The duodenum is the first section of the small intestine in most vertebrates, including mammals, reptiles, and birds. In mammals, it may be the principal site for iron absorption. The duodenum precedes the jejunum and ileum and is the shortest part of the small intestine. In humans, the duodenum is a hollow jointed tube about long connecting the stomach to the jejunum, the middle part of the small intestine. It begins with the duodenal bulb, and ends at the duodenojejunal flexure marked by the suspensory muscle of duodenum. The duodenum can be divided into four parts: the first (superior), the second (descending), the third (transverse) and the fourth (ascending) parts. Overview The duodenum is the first section of the small intestine in most higher vertebrates, including mammals, reptiles, and birds. In fish, the divisions of the small intestine are not as clear, and the terms ''anterior intestine'' or ''proximal intestine'' may be used instead of duodenum. In mammals the d ...
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Inflammation
Inflammation (from ) is part of the biological response of body tissues to harmful stimuli, such as pathogens, damaged cells, or irritants. The five cardinal signs are heat, pain, redness, swelling, and loss of function (Latin ''calor'', ''dolor'', ''rubor'', ''tumor'', and ''functio laesa''). Inflammation is a generic response, and therefore is considered a mechanism of innate immunity, whereas adaptive immunity is specific to each pathogen. Inflammation is a protective response involving immune cells, blood vessels, and molecular mediators. The function of inflammation is to eliminate the initial cause of cell injury, clear out damaged cells and tissues, and initiate tissue repair. Too little inflammation could lead to progressive tissue destruction by the harmful stimulus (e.g. bacteria) and compromise the survival of the organism. However inflammation can also have negative effects. Too much inflammation, in the form of chronic inflammation, is associated with variou ...
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Asymptomatic
Asymptomatic (or clinically silent) is an adjective categorising the medical conditions (i.e., injuries or diseases) that patients carry but without experiencing their symptoms, despite an explicit diagnosis (e.g., a positive medical test). Pre-symptomatic is the adjective categorising the time periods during which the medical conditions are asymptomatic. Subclinical and paucisymptomatic are other adjectives categorising either the asymptomatic infections (i.e., subclinical infections), or the psychosomatic illnesses and mental disorders expressing a subset of symptoms but not the entire set an explicit medical diagnosis requires. Examples An example of an asymptomatic disease is cytomegalovirus (CMV) which is a member of the herpes virus family. "It is estimated that 1% of all newborns are infected with CMV, but the majority of infections are asymptomatic." (Knox, 1983; Kumar et al. 1984) In some diseases, the proportion of asymptomatic cases can be important. For exam ...
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Cocaine- And Amphetamine-regulated Transcript
Cocaine- and amphetamine-regulated transcript, also known as CART, is a neuropeptide protein that in humans is encoded by the ''CARTPT'' gene. CART appears to have roles in reward, feeding, and stress, and it has the functional properties of an endogenous psychostimulant. Function CART is a neuropeptide that produces similar behavior in animals as cocaine and amphetamine, but conversely blocks the effects of cocaine when they are co-administered. The peptide is found in several areas, among them the ventral tegmental area (VTA) of the brain. When CART was injected into rat VTA, increased locomotor activity was seen, which is one of the signs of "central stimulation" caused by psychostimulants, such as cocaine and amphetamine. The same rats also tended to return to the place where they were injected. This is called conditioned place preference and is also seen after injection of cocaine. CART peptides, in particular, CART(55–102), seem to have an important function in ...
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Pro-opiomelanocortin
Pro-opiomelanocortin (POMC) is a precursor polypeptide with 241 amino acid residues. POMC is Protein biosynthesis, synthesized in Corticotropic cell, corticotrophs of the anterior pituitary from the 267-amino-acid-long Precursor polypeptide, polypeptide precursor pre-pro-opiomelanocortin (pre-POMC), by the removal of a 26-amino-acid-long signal peptide sequence during translation (biology), translation. POMC is part of the central melanocortin system. Function POMC is cut (cleaved) to give rise to multiple peptide hormones. Each of these peptides is packaged in large dense-core vesicle (biology), vesicles that are released from the cells by exocytosis in response to appropriate stimulation: * Melanocyte-stimulating hormone, α-MSH produced by neurons in the ventromedial nucleus has important roles in the regulation of appetite (POMC neuron stimulation results in Hunger (motivational state), satiety.) and Human sexual activity, sexual behavior, while α-MSH secreted from the pa ...
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Agouti-related Peptide
Agouti-related protein (AgRP), also called agouti-related peptide, is a neuropeptide produced in the brain by the AgRP/NPY neuron. It is synthesized 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. Structure AgRP is a paracrine signaling molecule made of 112 amino acids (the gene product of 132 amino acids is processed by removal of the N-terminal 20-residue signal peptide domain). It was independently identified by two teams in 1997 based on its sequence similarity with agouti signalling peptide (ASIP), a protein synthesized in the skin controlling coat colour. AgRP is approximately 25% identical to ASIP. The murine homologue of AgRP consists of 111 amin ...
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Neuropeptide Y
Neuropeptide Y (NPY) is a 36 amino-acid neuropeptide that is involved in various physiological and homeostatic processes in both the central and peripheral nervous systems. It is secreted alongside other neurotransmitters such as GABA and glutamate.  In the autonomic system it is produced mainly by neurons of the sympathetic nervous system and serves as a strong vasoconstrictor and also causes growth of fat tissue. In the brain, it is produced in various locations including the hypothalamus, and is thought to have several functions, including: increasing food intake and storage of energy as fat, reducing anxiety and stress, reducing pain perception, affecting the circadian rhythm, reducing voluntary alcohol intake, lowering blood pressure, and controlling epileptic seizures. Function Neuropeptide Y has been identified as being synthesized in GABAergic neurons and to act as a neurotransmitter during cellular communication. Neuropeptide Y is expressed in interneurons ...
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Neuron
A neuron (American English), neurone (British English), or nerve cell, is an membrane potential#Cell excitability, excitable cell (biology), cell that fires electric signals called action potentials across a neural network (biology), neural network in the nervous system. They are located in the nervous system and help to receive and conduct impulses. Neurons communicate with other cells via synapses, which are specialized connections that commonly use minute amounts of chemical neurotransmitters to pass the electric signal from the presynaptic neuron to the target cell through the synaptic gap. Neurons are the main components of nervous tissue in all Animalia, animals except sponges and placozoans. Plants and fungi do not have nerve cells. Molecular evidence suggests that the ability to generate electric signals first appeared in evolution some 700 to 800 million years ago, during the Tonian period. Predecessors of neurons were the peptidergic secretory cells. They eventually ga ...
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Ventromedial Hypothalamus
The ventromedial nucleus of the hypothalamus (VMN, VMH or ventromedial hypothalamus) is a nucleus of the hypothalamus. In 2007, Kurrasch ''et al''. found that the ventromedial hypothalamus is a distinct morphological nucleus involved in terminating hunger, fear, thermoregulation, and sexual activity. This nuclear region is involved in the recognition of the feeling of fullness. Structure It has four subdivisions: * Anterior (VMHa) * Dorsomedial (VMHdm) * Ventrolateral (VMHvl) * Central (VMHc) These subdivisions differ anatomically, neurochemically, and behaviorally. Function The ventromedial nucleus (VMN) is most commonly associated with satiety. Early studies showed that VMN lesions caused over-eating and obesity in rats. However, the interpretation of these experiments was summarily discredited when Gold's research demonstrated that precision lesioning of the VMN did not result in hyperphagia. Nevertheless, numerous studies have shown that the immediacy of hyperphagia an ...
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Lateral Hypothalamus
The lateral hypothalamus (LH), also called the lateral hypothalamic area (LHA), contains the primary orexinergic nucleus within the hypothalamus that widely projects throughout the nervous system; this system of neurons mediates an array of cognitive and physical processes, such as promoting feeding behavior and arousal, reducing pain perception, and regulating body temperature, digestive functions, and blood pressure, among many others. Clinically significant disorders that involve dysfunctions of the orexinergic projection system include narcolepsy, motility disorders or functional gastrointestinal disorders involving visceral hypersensitivity (e.g., irritable bowel syndrome), and eating disorders. The neurotransmitter glutamate and the endocannabinoids (e.g., anandamide) and the orexin neuropeptides orexin-A and orexin-B are the primary signaling neurochemicals in orexin neurons; pathway-specific neurochemicals include GABA, melanin-concentrating hormone, nociceptin, gluc ...
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Arcuate Nucleus
The arcuate nucleus of the hypothalamus (ARH), or ARC, is also known as the infundibular nucleus to distinguish it from the arcuate nucleus of the medulla oblongata in the brainstem. The arcuate nucleus is an aggregation of neurons in the mediobasal hypothalamus, adjacent to the third ventricle and the median eminence. The arcuate nucleus includes several important and diverse populations of neurons that help mediate different neuroendocrine and physiological functions, including neuroendocrine neurons, centrally projecting neurons, and astrocytes. The populations of neurons found in the arcuate nucleus are based on the hormones they secrete or interact with and are responsible for hypothalamic function, such as regulating hormones released from the pituitary gland or secreting their own hormones. Neurons in this region are also responsible for integrating information and providing inputs to other nuclei in the hypothalamus or inputs to areas outside this region of the brain. T ...
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