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)

The prevalence of obesity has reached epidemic proportions worldwide and the incidence of overweight and obesity continues to rise. Diet plays a significant role in the modulation of body weight and there is some evidence to suggest that calcium or dairy intake may modulate body weight and body fat mass. Several mechanisms through which calcium or dairy products may affect body weight or fat have been suggested, including a possible effect on appetite and food intake. A recent study investigated to what extent people could compensate for increased energy intake from dairy products and found that a 7-day increase in dairy intake had no effect on appetite and no evidence of complete compensation for the raised energy intake. In another study, the effects of altered calcium content of a dairy-based test meal was evaluated in obese subjects; the findings indicated that although a higher calcium content of the meal reduced the extent of post-prandial chylomicron-associated triglyceridemia, there was no effect on appetite-related hormones (CCK, ghrelin, GLP-1, or PPY) or on energy intake from a subsequent ad libitum test meal. Thus, this new evidence does not support the hypothesis that high calcium or dairy intake reduces appetite or food intake.
 ...
PMID:Can the controversial relationship between dietary calcium and body weight be mechanistically explained by alterations in appetite and food intake? 1882 56

Risk of developing obesity and diabetes may be influenced by the nutritional environment early in life. We examined the effects of high fibre or protein diets on satiety hormones and genes involved in glucose and lipid metabolism during postnatal development and on adult fat mass. At 21 days of age, Wistar rat pups were weaned onto control (C), high fibre (HF) or high protein (HP) diet. Tissue and blood were collected at 7, 14, 21, 28 and 35 days after birth. A second group of rats consumed the weaning diets until 4 months when they were switched to a high fat-high sugar diet for 6 weeks, after which body and fat mass and plasma glucose were determined. In young rats, HF diet increased plasma glucagon-like peptide (GLP-1) compared to C and HP and decreased leptin compared to C at postnatal days 28 and 35. Hepatic fatty acid synthase mRNA was down-regulated by HF and HP compared to C at days 28 and 35. In brown adipose tissue, HF increased uncoupling protein-3 mRNA whereas HP increased mRNA of the inflammatory cytokine interleukin-6. Body weight, fat mass and glycaemia in adult males and fat mass in females were greater after the high fat challenge in rats that consumed the HP diet from weaning. Increasing fibre or protein in postnatal diets causes rapid change in satiety hormone secretion and genes involved in glucose and lipid metabolism which appear to influence fat mass and glycaemia in adulthood, high protein being associated with increased susceptibility to obesity.
 ...
PMID:Changes in satiety hormones and expression of genes involved in glucose and lipid metabolism in rats weaned onto diets high in fibre or protein reflect susceptibility to increased fat mass in adulthood. 1906 20

Bariatric surgery is currently the most effective method to promote major, sustained weight loss. Roux-en-Y gastric bypass (RYGB), the most commonly performed bariatric operation, ameliorates virtually all obesity-related comorbid conditions, the most impressive being a dramatic resolution of type 2 diabetes mellitus (T2DM). After RYGB, 84% of patients with T2DM experience complete remission of this disease, and virtually all have improved glycemic control. Increasing evidence indicates that the impact of RYGB on T2DM cannot be explained by the effects of weight loss and reduced energy intake alone. Weight-independent antidiabetic actions of RYGB are apparent because of the very rapid resolution of T2DM (before weight loss occurs), the greater improvement of glucose homeostasis after RYGB than after an equivalent weight loss from other means, and the occasional development of very late-onset, pancreatic beta-cell hyperfunction. Several mechanisms probably mediate the direct antidiabetic impact of RYGB, including enhanced nutrient stimulation of L-cell peptides (for example, GLP-1) from the lower intestine, intriguing but still uncharacterized phenomena related to exclusion of the upper intestine from contact with ingested nutrients, compromised ghrelin secretion, and very probably other effects that have yet to be discovered. Research designed to prioritize these mechanisms and identify potential additional mechanisms promises to help optimize surgical design and might also reveal novel pharmaceutical targets for diabetes treatment.
 ...
PMID:Endocrine mechanisms mediating remission of diabetes after gastric bypass surgery. 1936 6

The function of the stomach and the gut hormonal responses to food ingestion constitute highly integrated homeostatic responses that maintain euglycemia and normal digestion. This intrinsic feedback involves vagal and hormonal mechanisms. Important signals such as GLP-1 and PYY that arise peripherally induce satiation and also delay gastric emptying or increase insulin secretion. Novel therapies are being developed to mimic or enhance these feedback mechanisms and to control appetite as a means to treat obesity.
 ...
PMID:Peripheral mechanisms in the control of appetite and related experimental therapies in obesity. 1940 36

We investigated a possible role of the central glucagon-like peptide (GLP-1) receptor system as an essential brain circuit regulating adiposity through effects on nutrient partitioning and lipid metabolism independent from feeding behavior. Both lean and diet-induced obesity mice were used for our experiments. GLP-1 (7-36) amide was infused in the brain for 2 or 7 d. The expression of key enzymes involved in lipid metabolism was measured by real-time PCR or Western blot. To test the hypothesis that the sympathetic nervous system may be responsible for informing adipocytes about changes in CNS GLP-1 tone, we have performed direct recording of sympathetic nerve activity combined with experiments in genetically manipulated mice lacking beta-adrenergic receptors. Intracerebroventricular infusion of GLP-1 in mice directly and potently decreases lipid storage in white adipose tissue. These effects are independent from nutrient intake. Such CNS control of adipocyte metabolism was found to depend partially on a functional sympathetic nervous system. Furthermore, the effects of CNS GLP-1 on adipocyte metabolism were blunted in diet-induced obese mice. The CNS GLP-1 system decreases fat storage via direct modulation of adipocyte metabolism. This CNS GLP-1 control of adipocyte lipid metabolism appears to be mediated at least in part by the sympathetic nervous system and is independent of parallel changes in food intake and body weight. Importantly, the CNS GLP-1 system loses the capacity to modulate adipocyte metabolism in obese states, suggesting an obesity-induced adipocyte resistance to CNS GLP-1.
 ...
PMID:Direct control of peripheral lipid deposition by CNS GLP-1 receptor signaling is mediated by the sympathetic nervous system and blunted in diet-induced obesity. 1942 Feb 58

Obesity is now classically characterized by a cluster of several metabolic disorders, and by a low grade inflammation. The evidence that the gut microbiota composition can be different between healthy and or obese and type 2 diabetic patients has led to the study of this environmental factor as a key link between the pathophysiology of metabolic diseases and the gut microbiota. Several mechanisms are proposed linking events occurring in the colon and the regulation of energy metabolism, such as i.e. the energy harvest from the diet, the synthesis of gut peptides involved in energy homeostasis (GLP-1, PYY...), and the regulation of fat storage. Moreover, the development of obesity and metabolic disorders following a high-fat diet may be associated to the innate immune system. Indeed, high-fat diet feeding triggers the development of obesity, inflammation, insulin resistance, type 2 diabetes and atherosclerosis by mechanisms dependent of the LPS and/or the fatty acids activation of the CD14/TLR4 receptor complex. Importantly, fat feeding is also associated with the development of metabolic endotoxemia in human subjects and participates in the low-grade inflammation, a mechanism associated with the development of atherogenic markers. Finally, data obtained in experimental models and human subjects are in favour of the fact that changing the gut microbiota (with prebiotics and/or probiotics) may participate in the control of the development of metabolic diseases associated with obesity. Thus, it would be useful to find specific strategies for modifying gut microbiota to impact on the occurrence of metabolic diseases.
 ...
PMID:The role of the gut microbiota in energy metabolism and metabolic disease. 1944 72

Incretin-based therapies address the progressive nature of type 2 diabetes mellitus, not only by addressing glucose control but also with weight-neutral (i.e., dipeptidyl peptidase-4 inhibitors sitagliptin and vildagliptin) and weight-reducing effects (i.e., glucagonlike peptide-1 [GLP-1] receptor agonists exenatide and liraglutide). Preclinical data suggest that incretin-based therapies may also preserve beta-cell function, holding promise of a truly disease-modifying therapy. This article examines clinical trial data and accepted algorithms with a view toward elucidating the application of these agents in routine clinical practice. We propose a systematic approach to treatment, addressing (1) patient selection, (2) optimal treatment combinations, and (3) timing and guidance for both initiation and intensification of therapy. The GLP-1 receptor agonists, for example, could be particularly beneficial in patients whose weight significantly increases cardiovascular risk. Early use of these agents may be effective in preventing diabetes in those at risk, or in halting or retarding disease progression in patients with frank diabetes. Additional clinical investigation will be required to test such hypotheses. Given the ever-increasing incidence of diabetes worldwide, the link between obesity and the development of type 2 diabetes, and the need for more effective, weight-focused, convenient and sustainable treatments, the data from such studies will be invaluable to further clarify the role of the incretins in the management of patients with type 2 diabetes.
 ...
PMID:Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. 1946 27

Type 2 diabetes (T2D) and associated obesity have reached epidemic proportions, and there is an increasing need for orally effective agents that regulate glucose homeostasis with a concurrent reduction in body weight. GPR119, a class-A (rhodopsin-like) G protein-coupled receptor, expressed primarily in the human pancreas and gastrointestinal tract, has attracted considerable interest as a T2D drug target in the last three to five years. The activation of GPR119 increases the intracellular accumulation of cAMP, leading to enhanced glucose-dependent insulin secretion and increased levels of the incretin hormones GLP-1 (glucagon-like peptide 1) and GIP (glucose-dependent insulinotropic peptide). In rodent models, orally available GPR119-specific agonists have been shown to attenuate blood glucose levels with a simultaneous body weight loss. This review summarizes the research leading to the identification of GPR119 as a potential drug target for T2D and related metabolic disorders. In addition, an overview of the recent progress made in the discovery of orally active GPR119 agonists is provided.
 ...
PMID:GPR119 agonists: a promising new approach for the treatment of type 2 diabetes and related metabolic disorders. 1956 48

Available therapies for type 2 diabetes are not always satisfactory because they do not address the problems of overweight/obesity and the progressive deterioration of cell function. GLP-1 analogues or agonists of the GLP-1 receptor are a new therapeutic option which offer promises; they indeed improve glycemic control, decrease weight by 2-3 kg/year and may stabilize or improve cell function by favoring cell proliferation and inhibiting apoptosis. Their use in patients who are not sufficiently controlled by metformin and sulfonylurea compares favourably to insulin treatment.
 ...
PMID:[Role and indication of GLP-1 analogues in the treatment of type 2 diabetes]. 1957 21

Incretin-based therapies address the progressive nature of type 2 diabetes mellitus, not only by addressing glucose control but also with weight-neutral (i.e., dipeptidyl peptidase-4 inhibitors sitagliptin and vildagliptin) and weight-reducing effects (i.e., glucagonlike peptide-1 [GLP-1] receptor agonists exenatide and liraglutide). Preclinical data suggest that incretin-based therapies may also preserve beta-cell function, holding promise of a truly disease-modifying therapy. This article examines clinical trial data and accepted algorithms with a view toward elucidating the application of these agents in routine clinical practice. We propose a systematic approach to treatment, addressing (1) patient selection, (2) optimal treatment combinations, and (3) timing and guidance for both initiation and intensification of therapy. The GLP-1 receptor agonists, for example, could be particularly beneficial in patients whose weight significantly increases cardiovascular risk. Early use of these agents may be effective in preventing diabetes in those at risk, or in halting or retarding disease progression in patients with frank diabetes. Additional clinical investigation will be required to test such hypotheses. Given the ever-increasing incidence of diabetes worldwide, the link between obesity and the development of type 2 diabetes, and the need for more effective, weight-focused, convenient and sustainable treatments, the data from such studies will be invaluable to further clarify the role of the incretins in the management of patients with type 2 diabetes.
 ...
PMID:Clinical application of incretin-based therapy: therapeutic potential, patient selection and clinical use. 1958 Sep 52


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