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Query: UMLS:C0028754 (obesity)
 124,988 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

In patients with type 2 non-insulin-dependent diabetes mellitus (NIDDM), the biguanide, metformin, exerts its antihyperglycemic effect by improving insulin sensitivity, which is associated with decreased level of circulating free fatty acids (FFA). The flux of FFA and glycerol from adipose tissue to the blood stream primarily depends on the lipolysis of triacylglycerols in the adipocytes. Adipocyte lipolysis is physiologically stimulated by catecholamine hormones. Tumor necrosis factor-alpha (TNF-alpha), a cytokine largely expressed in adipose tissue, stimulates chronic lipolysis, which may be associated with increased systemic FFA and insulin resistance in obesity and NIDDM. In this study, we examined the role of metformin in inhibiting lipolytic action upon various lipolytic stimulations in primary rat adipocytes. Treatment with metformin attenuated TNF-alpha-mediated lipolysis by suppressing phosphorylation of extracellular signal-related kinase 1/2 and reversing the downregulation of perilipin protein in TNF-alpha-stimulated adipocytes. The acute lipolytic response to adrenergic stimulation of isoproterenol was also restricted by metformin. A high concentration of glucose in the adipocyte culture promoted the basal rate of glycerol release and significantly enhanced the lipolytic action stimulated by either TNF-alpha or isoproterenol. Metformin not only inhibits the basal lipolysis simulated by high glucose, but also suppresses the high glucose-enhanced lipolysis response to TNF-alpha or isoproterenol. The antilipolytic action in adipocytes could be the mechanism by which cellular action by metformin reduces systemic FFA concentration and thus improves insulin sensitivity in obese patients and the hyperglycemic conditions of NIDDM.
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PMID:Metformin reduces lipolysis in primary rat adipocytes stimulated by tumor necrosis factor-alpha or isoproterenol. 1690 33

Polycystic ovary syndrome was defined as the combination of anovulation and hyperandrogenaemia (NIH 1990). Another definition used the combination of ultrasonographic appearance of polycystic ovaries and/or anovulation and/or hyperandrogenaemia or cutaneous manifestations of hyperandrogenism (Rotterdam). The population defined according to NIH is probably in greater risk of insulin resistance and obesity. Pathogenesis of PCOS is not clear till now. Dysregulation of ovarian steroidogenesis could be one of the causes of the full-blown syndrome. Up-regulation of steroidogenic enzymes, probably due to the exaggerated expression of transcription factors such as GATA-6 or retinoids could be involved. Insulin sensitisators are now widely used in the therapy. They could beneficially modify not only insulin resistance and dyslipidaemia, but also ovarian and adrenal steroidogenesis. Metformin and glitazones improve anovulation however the studies conducted till now were not representative concerning the point of successful pregnancy.
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PMID:[Polycystic ovary syndrome in 2006]. 1741 3

Polycystic ovary syndrome (PCOS) is one of the most common endocrinopathies in reproductive-age women. It often presents during late adolescence but in some cases certain features are evident even before menarche. PCOS is a spectrum of disorders with any combination of oligo/anovulation, clinical and/or biochemical evidence of androgen excess, obesity, insulin resistance and polycystic ovaries on ultrasound. The pathogenesis is unknown; however, it is a complex multigenetic disorder where disordered gonadotropin release, dysregulation of steroidogenesis, hyperinsulinism and insulin resistance play a role. The diagnosis is based on a typical physical exam (acne, hirsutism, obesity, and acanthosis nigricans) and laboratory evidence of hyperandrogenism, such as elevated free testosterone, androstenedione and dehydroepiandrosterone sulfate (DHEAS), decreased sex hormone-binding globulin (SHBG) and increased luteinizing hormone (LH). An ovarian ultrasound may detect the multiple cysts. Secondary causes of PCOS need to be excluded. There are several classes of medications correcting different parameters of PCOS that can be used alone or in combination. Oral contraceptive therapy is used to reduce androgen and LH levels with resultant improvement in acne and hirsutism, and the induction of regular menses. Antiandrogens are usually required for a substantial improvement in hirsutism score. Insulin sensitizers such as metformin are a new class of drugs utilized in treatment of PCOS. By improving insulin sensitivity and decreasing insulin levels, they improve the unfavorable metabolic profile of patients with PCOS. Metformin also helps to increase SHBG, decrease androgen levels and induce ovulation. Despite all the available medications, life-style changes are the mainstay of therapy as weight loss and exercise improve all parameters of PCOS without the potential side effects of medication.
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PMID:Current approaches to the diagnosis and treatment of polycystic ovarian syndrome in youth. 1742 8

To investigate the relative role of the adiponectin and leptin in the insulin resistance (IR) and obesity we studied plasma levels of these adipocytokines in obese and insulin resistant postmenopausal (PM) females with type 2 diabetes (DM2) during 6 months of Metformin therapy. We recruited 26 PM women, between the ages of 50 and 67 (59,7+/-8,1 years). These women had a BMI of 36,6+/-1,8 kg/m2. After baseline measurements Metformin therapy has been initiated (1700+/-2550 mg per day). Duration of therapy was 6 months. The results of investigations of adipocytokines after Metformin 6 months therapy shown that circulating adiponectin levels were significantly increased (19,1+/-6,0 vs. 16,1+/-3,9 ng/ml, p=0,008) together with significant reduction of BMI (35,9+/-1,9 vs. 36,6+/-1,8 kg/m2, p=0,005) and IR (3,05+/-0,89 vs. 3,96+/-0,70, p<0,001). The magnitude of the change in adiponectin levels positively correlated with the magnitude of BMI reduction (r=0,4784, p=0,013) and IR reduction (r=0,5779, p=0,002). Any significant correlation did not observed between changes of leptin levels and BMI, leptin levels and IR. In summary, our data suggest that hypoadiponectinemia in PM may be explained by only IR because the amelioration of whole-body insulin action by 6-month Metformin therapy leads to increase of plasma adiponectin levels; leptin levels did not significantly change after 6-month Metformin therapy.
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PMID:Effect of metformin therapy on plasma adiponectin and leptin levels in obese and insulin resistant postmenopausal females with type 2 diabetes. 1752 1

Most patients with type 2 diabetes are overweight or obese, overweight or obesity increases the risk of developing type 2 diabetes and obesity per se is strongly associated with multiple cardiometabolic risk factors. However, many antidiabetic treatments increase body weight. The oral antidiabetic agent, metformin, has been evaluated in hundreds of clinical studies in diverse patient populations during approximately five decades of clinical use. This review summarizes the effects of metformin on body weight, with special reference to studies of longer duration (>/=6 months) as both diabetes and obesity are long-term conditions. Approximately half of studies in drug-naive type 2 diabetic patients demonstrated significant weight loss with metformin compared with baseline or comparator drugs, although pooled analyses have suggested no significant effect versus placebo. Similarly, metformin has been shown to induce weight loss in obese nondiabetic populations, although studies of long duration in this population are scarce. Metformin does appear to mitigate the adverse effects of insulin on body weight. The weight-neutral or weight-sparing effects of metformin constitute a therapeutic advantage in diabetes management where other first-line oral antidiabetic treatments often promote clinically significant weight gain.
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PMID:Metformin and body weight. 1765 63

The case of a 35-year-old female patient who was diagnosed as schizophrenia treated with psychotrophic drugs nearly for 15 years is presented here. After the disease was diagnosed, the patient quit her university education and began to live inactively far from her social environment, usually spending lazy time at home. During this period, due to either the effects of drugs which have to be used on hormones affecting appetite and body weight or her decreased physical activity, her body weight increased by nearly 30 kg. Anthropometric measurements, biochemical parameters and food diaries were evaluated at the beginning of the nutritional counseling and then repeated periodically. Upon obtaining biochemical findings, collaboration with other units started. The patient was educated on nourishing healthy and controlling body weight, also to bring about lasting behavioral changes. At the beginning of the therapy, among the biochemical measurements, insulin resistance was defined and metformin treatment was begun. Metformin therapy contributed to the patient's adaptation to the diet and improved glucose tolerance. In this way, it was possible to cope with the insulin resistance caused by anti-psychotic pharmacotherapy (clozapine) and the obesity which had developed as a result of clozapine. During the 18-month therapy the patient lost 27 kg, her body fat was reduced by 10% (18 kg) and BMI returned to normal levels. It is known that, many medications used in psychiatric disorders affect appetite and body weight. As seen in our patient metformin therapy causes weight loss and decreases insulin resistance. Both the illness and the medications used for treatment could affect the hormones which play a part in controlling body weight and the cytokines, as a result could change food preference and eating behavior which ultimately pave the way to obesity.
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PMID:Nutritional approach to metabolic changes arising out of schizophrenia therapy: case report. 1767 72

Excessive supply of fatty acids to the liver might be a contributing factor to hepatic insulin resistance associated with obesity and type 2 diabetes mellitus. The aim of this study was to investigate direct effects of palmitate on insulin signaling in hepatocytes. The ability of metformin to reverse changes induced by palmitate was also studied. Rat hepatocytes in primary culture exhibited a rightward shift of the insulin dose-response curve for PKB phosphorylation during culture with palmitate. The insulin-stimulated phosphorylation of GSK-3beta, a metabolic substrate of PKB, was diminished in palmitate hepatocytes. By contrast, the mTOR protein kinase was overstimulated in cells incubated with palmitate. Hepatocytes cultured with palmitate displayed hyperphosphorylation of IRS-1 at Ser residues 632/635, known to be phosphorylated by mTOR. Metformin treatment of the hepatocytes resulted in activation of the AMP-activated kinase, attenuation of the mTOR/S6K1 pathway, reduction of IRS-1 phosphorylation, and a leftward shift in the insulin dose-response curve for PKB activation. These data suggest a link between an oversupply of fatty acid to hepatocytes, a disproportionate stimulation of mTOR/S6K1, and resistance to insulin.
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PMID:Activation of mammalian target of rapamycin complex 1 and insulin resistance induced by palmitate in hepatocytes. 1769 34

The metabolic syndrome (MS), a cluster of risk factors, such as obesity, hyperglycemia, hypertension and dyslipidemia, contributes to the development of cardio-vascular diseases and type 2 diabetes mellitus (DM2). Insulin resistance (IR) plays a key role in MS being strongly linked to abdominal visceral fat. Treatment for obese patients with MS should aim at improving IR, delaying the onset of DM2 and at reducing cardio-vascular risk. Weight loss, first therapeutic target, may be obtained through life-style modifications and anti-obesity drugs or bariatric surgery, at need. In these patients drug therapy is necessary if therapeutic life-style changes are not sufficient. Some drugs have adverse metabolic effects, therefore the therapeutic choices must be specific and rational. Metformin, Thiazolidinediones and Acarbose are anti-hyperglycemic drugs of choice: they reduce the incidence of DM2 and IR (or improve insulin sensitivity) and they decrease or stabilize the visceral adipose tissue mass (Thiazolidinediones increases subcutaneous fat only). Also Angiotensin II receptor blockers and Angiotensin-converting enzyme inhibitors reduce the incidence of DM2 and insulin resistance and they are first-line antihypertensive drugs in MS. Calcium channel blockers, Alpha-1 antagonists and Alpha-2 agonists drugs are metabolically neutral and slight weight gains are related to the hydro-sodium retention. Beta-blockers and Diuretics, except for Indapamide and Anti-aldosterone drugs, can reduce insulin sensitivity, impair lipid profile and increase DM2 incidence; they are not first-line therapy yet they are necessary in selected cases only. Statins, Fibrates and omega-3 Fatty acids are indicated to normalize dyslipidemia. Low doses of acetylsalicylic acid are also recommended.
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PMID:[Therapeutic options for metabolic syndrome in obese patients]. 1806 54

Chronic exposure to glucocorticoid hormones, resulting from either drug treatment or Cushing's syndrome, results in insulin resistance, central obesity, and symptoms similar to the metabolic syndrome. We hypothesized that the major metabolic effects of corticosteroids are mediated by changes in the key metabolic enzyme adenosine monophosphate-activated protein kinase (AMPK) activity. Activation of AMPK is known to stimulate appetite in the hypothalamus and stimulate catabolic processes in the periphery. We assessed AMPK activity and the expression of several metabolic enzymes in the hypothalamus, liver, adipose tissue, and heart of a rat glucocorticoid-excess model as well as in in vitro studies using primary human adipose and primary rat hypothalamic cell cultures, and a human hepatoma cell line treated with dexamethasone and metformin. Glucocorticoid treatment inhibited AMPK activity in rat adipose tissue and heart, while stimulating it in the liver and hypothalamus. Similar data were observed in vitro in the primary adipose and hypothalamic cells and in the liver cell line. Metformin, a known AMPK regulator, prevented the corticosteroid-induced effects on AMPK in human adipocytes and rat hypothalamic neurons. Our data suggest that glucocorticoid-induced changes in AMPK constitute a novel mechanism that could explain the increase in appetite, the deposition of lipids in visceral adipose and hepatic tissue, as well as the cardiac changes that are all characteristic of glucocorticoid excess. Our data suggest that metformin treatment could be effective in preventing the metabolic complications of chronic glucocorticoid excess.
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PMID:AMP-activated protein kinase mediates glucocorticoid-induced metabolic changes: a novel mechanism in Cushing's syndrome. 1819 20

Obesity is a risk factor for asthma. The purpose of this study was to determine whether metformin, an agent used in the treatment of an obesity-related condition (type II diabetes), might have therapeutic potential for modifying the effects of obesity on airway smooth muscle (ASM) function. Metformin acts via activation of AMP-activated protein kinase (AMPK), a cellular sensor of energy status. In cultured murine ASM cells, metformin (0.2-2 mM) caused a dose-dependent inhibition of cell proliferation induced by PDGF (10(-8) M) and serotonin (10(-4) M). Another AMPK activator, 5-aminoimidazole-4-carboxamide-1-beta-Driboruranoside (AICAR), also inhibited PDGF-induced proliferation. Furthermore, cells treated with metformin or AICAR, also exhibited an attenuation in the rate of cytoskeletal remodeling, as quantified by spontaneous nanoscale motions of microbeads tightly anchored to the cytoskeleton (CSK) of the ASM cell. ASM cells treated with metformin or AICAR, however, exhibited no appreciable differences in stiffness as measured by optical magnetic twisting cytometry (OMTC) or their abilities to stiffen in response to contractile agonist serotonin. Taken together, these findings suggest that metformin, probably through activation of AMPK, reduces the rate of ongoing reorganization of the CSK and inhibits ASM cell proliferation.
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PMID:Airway smooth muscle proliferation and mechanics: effects of AMP kinase agonists. 1832 Sep 1


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