Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Neurons of the arcuate nucleus of the hypothalamus (ARH) appear to be sites of convergence of central and peripheral signals of energy stores, and profoundly modulate the activity of the melanocortin circuits, providing a strong rationale for pursuing these circuits as therapeutic targets for disorders of energy homeostasis. Recently, tremendous advances have been made in identifying genes and pathways important to regulating energy homeostasis, particularly the hormone leptin and its receptor. This hormone/receptor pair is expressed at high levels in the so-called satiety centers in the hypothalamus, and at lower levels elsewhere in the body. Recent studies in our lab and those of our collaborators have shown that leptin modulates different populations of hypothalamic cells in different ways, rapidly activating POMC neurons and inhibiting NPY/AgRP neurons. In this report, we outline an integrated model of leptin's action in the arcuate nucleus of the hypothalamus, derived from our electrophysiological studies of brain slice preparations taken from transgenic mice that have been bred to express a variety of fluorescent proteins in specific cell types. We also discuss the recently withdrawn obesity drug fenfluramine, which appears to act on POMC neurons via the serotonin 2C receptor. Nutrient-sensing serotonin neurons may project from the raphe nuclei in the brainstem to the hypothalamus; within the arcuate nucleus, serotonin signals are integrated with others such as leptin, ghrelin, and peptide YY(3-36) from the gut, to produce a coordinated response to nutrient state. Finally, we review the current inquiries into the ability of the hormone ghrelin to stimulate appetite by its action of NPY neurons and inhibition of POMC neurons.
 ...
PMID:Electrophysiological actions of peripheral hormones on melanocortin neurons. 1285 14

The Scopinaro surgical technique for obesity consists of a partial distal gastrectomy with biliopancreatic diversion and cholecystectomy. It is an effective procedure in the control of the body weight but disrupts the physiological gut-liver axis. We report the case of a patient who developed liver cirrhosis with a multifactorial pathogenesis following antiobesity surgery according to Scopinaro and discuss the pathogenesis of the liver damage on the basis of our present understanding of alcoholic and nonalcoholic steatohepatitis. A 41-year-old male patient presented with ascites due to cryptogenic liver cirrhosis. Owing to morbid obesity, he had undergone antiobesity surgery according to Scopinaro when he was 25 years old. The procedure was effective and the patient lost about 40 kg of weight but manifested chronic diarrhea in the postoperative course. During the following 15 years, the patient continued to assume 100 g alcohol/day and did not turn up for clinical evaluation. Signs and symptoms of liver failure appeared in May 2000. After surgical correction of biliopancreatic diversion and abstinence from alcohol the hepatocellular function partially recovered and the patient regained his subjective complete well-being. The multifactorial pathogenesis of the liver disease observed in our patient included obesity, antrectomy, heavy alcohol consumption, bacterial overgrowth, and protein malnutrition.
 ...
PMID:[Multifactorial hepatopathy in a patient with biliopancreatic diversion]. 1288 27

The gastrointestinal tract and the pancreas release hormones regulating satiety and body weight. Ghrelin stimulates appetite, and glucagon-like peptide-1, oxyntomodulin, peptide YY, cholecystokinin, and pancreatic polypeptide inhibit appetite. These gut hormones act to markedly alter food intake in humans and rodents. Obesity is the current major cause of premature death in the United Kingdom, killing almost 1000 people per week. Worldwide, its prevalence is accelerating. There is currently no effective answer to the pandemic of obesity, but replacement of the low levels of peptide YY observed in the obese may represent an effective antiobesity therapy.
 ...
PMID:Minireview: Gut peptides regulating satiety. 1504 53

Physical activity has been shown to reduce risk of colon cancer. Some studies have shown site-specific associations while others have not. The inverse association between physical activity and colon cancer is consistent although only 7 of 13 studies that have collected both colon and rectal cancer data in the same manner report reduced risk for rectal cancer; four of these studies detected statistically significant inverse associations. The frequency, duration and intensity of activity are important components of a public health message to reduce risk of colon cancer through performance of physical activity. However, difficulties in estimating the exact amount of activity needed and frequency and intensity of activity result in only crude estimates of dose needed for a protective effect. Much of the literature suggest that more intense activity is needed to reduce colon cancer risk and that somewhere between 3.5 and 4 hours of vigorous activity per week may be needed to optimise protection. Several biological mechanisms have been proposed to explain the association between physical activity and colon cancer; many of these mechanisms also support the observation that intense activities are most protective. Biological mechanisms include: physical activity increasing gut motility; enhancing the immune system; decreasing insulin and insulin-like growth factor levels; decreasing obesity; enhancing free radical scavenger systems; and influencing prostaglandin levels. The evidence taken together provides strong support for lack of physical activity being causally related to colon cancer. It has been estimated that 12-14% of colon cancer could be attributed to lack of frequent involvement in vigorous physical activity.
 ...
PMID:Physical activity and colorectal cancer. 1504 16

Obesity is a major health problem and as a result, it is reasonable to consider pharmacological approaches alongside approaches involving diet, physical activity and lifestyle change. The currently available drugs, sibutramine and orlistat, result in modest, clinically worthwhile weight loss, with demonstrable improvements in co-morbidity, but do not meet the often unrealistic expectations of patients or health care professionals managing obese patients. There is insufficient data on efficacy or safety of other agents to support their use. Many new pharmacological approaches are under investigation. These include gut hormones, such a peptide YY (3-36) and cholecystokinin that normally signal satiety, and centrally-acting agents such as serotonin agonists, the anticonvulsants topiramate and zonisamide, cannabinoid receptor antagonists and drugs that act on other peptide neurotransmitter systems such as NPY and the melanocortins. Given the multiple pathways that influence energy balance, it is likely that therapies targeting more than one control system may be required in the future to meet the expectations and needs of patients needing to lose weight for medical reasons.
 ...
PMID:Clinical evaluation of anti-obesity drugs. 1505 16

Gastrointestinal tract (GIT) and nervous system, both central (CNS) and enteric (ENS), are involved in two-way extrinsic communication by parasympathetic and sympathetic nerves, each comprising efferents fibers such as cholinergic and noradrenergic, respectively, and afferent sensory fibers required for gut-brain signaling. Afferent nerves are equipped with numerous sensors at their terminals in the gut related to visceral mechano- chemo- and noci-receptors, whose excitations may trigger a variety of visceral reflexes regulating GIT functions, including the appetitive behaviour. Food intake depends upon various influences from the CNS as well as from the body energy stores (adipocytes) that express and release the product of Ob gene, leptin, in proportion to fat stored and acting in long-term regulation of food intake. Leptin acts through receptors (Ob-R) present in afferent visceral nerves and hypothalamic arcuate nucleus (ARC), whose neurons are capable of expressing and releasing neuropeptide Y (NPY) and agouti related protein (AgRP) that activate the ingestive behaviour through paraventricular nucleus (PVN) (iVfeeding centerli). In addition, to this long-term regulation, a short-term regulation, on meal-to-meal basis, is secured by several gut hormones, such as cholecystokinin (CCK), peptides YY (PYY) and oxyntomodulin (OXM), released from the endocrine intestinal cells and acting via G-protein coupled receptors (GPCR) either on afferent nerves or directly on ARC neurons, which in turn inhibit expression and release of food-intake stimulating NPY and AgRP, thereby inducing satiety through inhibition of PVN. In contrast, during fasting, the GIT, especially oxyntic mucosa, expresses and releases appetite stimulating (orexigenic) factors such as ghrelin and orexins (OX) -A and OX-B, and cannabinoid CB1 agonist. Ghrelin activates growth-hormone secretagogue receptor (GHS-R) in hypothalamic ARC and stimulates growth hormone (GH) release and in vagal afferents to promote the expression and release of hypothalamic NPY and AgRP stimulating PVN and driving ingestive behaviour. The balance and interaction between anorexigenic (CCK, PYY, OXM) and orexigenic (ghrelin and OX) factors originating from GIT appears to play an important role in short-term regulation of food intake and growth hormone (GH) release. An impairment of this balance may result in disorders of feeding behaviour and weight gain (obesity) or weight loss (cachexia).
 ...
PMID:Brain-gut axis and its role in the control of food intake. 1508 74

Signals generated by the gastrointestinal tract are able to regulate appetite and influence body weight. Ghrelin is an orexigenic peptide produced by the stomach. Satiety signals derived from the intestine and pancreas include peptide YY, pancreatic polypeptide, glucagon-like peptide 1, oxyntomodulin, and cholecystokinin. Signals from the gut and adipose tissue are integrated in the central nervous system to provide energy homeostasis. Knowledge of the body's control of appetite is important because we strive to combat obesity in man.
 ...
PMID:The gut and regulation of body weight. 1518 Oct 26

Obesity is one of the greatest threats to the health of the developed world. In order to design effective drugs to treat the alarming increase in obesity, it is essential to understand the physiology of normal appetite control and the pathophysiology of obesity. The hypothalamus interprets and integrates neural and humoral inputs to provide a coordinated feeding and energy expenditure response. Recent evidence suggests that certain gut hormones - ghrelin, polypeptide YY, pancreatic polypeptide, glucagon-like-peptide 1 and oxyntomodulin - have a physiological role in governing satiety via the hypothalamus. Gut hormone appetite-regulatory systems represent a potential target for the design of antiobesity drugs.
 ...
PMID:Gut hormones in the control of appetite. 1518 57

The past decade has witnessed a dramatic acceleration in research on the role of the neuropeptides in the regulation of eating behavior and body weight homeostasis. This expanding research focus has been driven in part by increasing public health concerns related to obesity and the eating disorders anorexia nervosa (AN) and bulimia nervosa (BN). Preclinical advances have been facilitated by the development of new molecular and behavioral research methodologies. With a focus on clinical investigations in AN and BN, this article reviews research on selected hypothalamic and gut-related peptide systems with prominent effects on eating behavior. Studies of the orexigenic peptides neuropeptide Y and the opioid peptides have shown state-related abnormalities in patients with eating disorders. With respect to gut-related peptides, there appears to be substantial evidence for blunting in the meal-related release of the satiety promoting peptide cholecystokinin in BN. Fasting plasma levels of the orexigenic peptide ghrelin have been found to be elevated in patients with AN. As discussed in this review, additional studies will be needed to assess the role of nutritional and body weight changes in neuropeptide alterations observed in symptomatic eating disorder patients, and to identify stable trait-related abnormalities in neuropeptide regulation that persist in individuals who have recovered from an eating disorder.
 ...
PMID:Neuropeptides in eating disorders. 1520 11

New information regarding gastrointestinal mechanisms that participate in the control of food intake has extended our understanding of appetite control. Although each new signaling pathway discovered in the gut is a potential target for drug development in the treatment of obesity, the growing number of such signaling molecules indicates that a highly complex process controls food intake. The present summary focuses on the role of glucagon-like peptide 1 (GLP-1) in this regulatory process. The different biological effects of GLP-1 (glucose-lowering properties, inhibition of appetite and food intake) provide a powerful impetus for development of GLP-1-based new drugs.
 ...
PMID:Glucagon-like peptide 1 (GLP-1) and eating. 1523 84


<< Previous 1 2 3 4 5 6 7 8 9 10 Next >>