Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The lipolysis in adipose tissue is controlled by the hormone-sensitive lipase activity which is dependent on the intracellular cAMP level. In human adipose tissue, cAMP level is increased by catecholamines (through beta-adrenoceptor stimulation) or decreased by insulin, catecholamine (through alpha 2-adrenoceptor stimulation), neuropeptide Y, prostaglandins and adenosine. The mobilization of lipids from adipose tissue is an adaptative mechanism in response to starvation or hypocaloric diet, which involves reduction of the antilipolytic effect of insulin and the increase of catecholamine sensitivity. The regulatory pathways of lipolysis and their adaptation to caloric reduction are not defective in obesity state. Pharmacological approaches proposed for the activation of lipolysis are limited; they mainly consist either to stimulate the fat cell beta-adrenoceptors (beta-sympathomimetic drugs) or to indirectly activate the sympathetic nervous system (ephedrine and its derivatives, methylxanthines, alpha 2-antagonists). However, the side effects elicited by these drugs frequently limit their clinical use.
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PMID:[Lipid mobilization, physiopathological and pharmacological aspects]. 775 46

Positive caloric balance often causes pathologic adipocyte and adipose tissue anatomical and functional changes (termed adiposopathy or 'sick fat'), which may lead to pathogenic adipocyte and adipose tissue responses and metabolic disease. Fat weight loss may improve adiposopathy, and thus improve metabolic disease in overweight patients. Unfortunately, the efficacy of non-surgical weight loss therapies is often limited due to redundant physiological systems that help 'protect' against starvation and/or negative caloric balance. One strategy to overcome these limitations is to combine weight loss drug therapies having complementary mechanisms of action, thereby affecting more than one physiologic process influencing body fat accumulation. Phentermine is a noradrenergic sympathomimetic amine approved for short-term treatment of obesity. Topiramate is a sulfamate-substituted monosaccharide derivative of the naturally occurring sugar monosaccharide D-fructose approved as a treatment for migraine headaches and seizure disorders. Although known to facilitate weight loss since its approval, topiramate monotherapy does not have a regulatory indication as an anti-obesity agent. Phentermine HCl/topiramate controlled-release (PHEN/TPM CR) is a combination agent containing immediate-release phentermine and controlled-release topiramate. Clinical trials involving thousands of patients demonstrate PHEN/TPM CR to be effective in improving the weight of patients, and also effective in improving adiposopathy-associated metabolic diseases. This review examines the pathophysiology of adiposopathy as a contributor to metabolic disease, the data supporting phentermine monotherapy, topiramate monotherapy and their combination as anti-obesity and anti-adiposopathy agents, and the preliminary evidence supporting PHEN/TPM CR as a generally well-tolerated and effective agent to improve metabolic disease.
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PMID:Phentermine, topiramate and their combination for the treatment of adiposopathy ('sick fat') and metabolic disease. 2070 65