Effects of metformin on weight loss

Malin, Steven K.; Kashyap, Sangeeta R.

doi:10.1097/med.0000000000000095

Cited by 205 publications

(171 citation statements)

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“…Despite the known glucose-lowering effects of metformin, more recent clinical interest lies in its potential as a weight loss drug based primarily on its ability to stimulate a reduction in food intake. In addition to appetite suppression, metformin improves leptin sensitivity, changes gastrointestinal physiology, and regulates fat oxidation and storage [11]. Clinical studies revealed that metformin treatment of oligo-teratoasthenozoospermic men with metabolic syndrome obtained satisfactory effects, including significant reductions in insulin and sex-hormone-binding globulin levels, increased serum androgen levels, and a consequent improvement in semen characteristics [19].…”

Section: Discussionmentioning

confidence: 96%

“…Long-term follow-up from the Diabetes Prevention Program demonstrated that metformin produced durable weight loss in several ways, with decreased food intake shown to be the primary mechanism [11]. Clinical trials showed that the mean total and free testosterone levels increased significantly after metformin treatment in men with metabolic syndrome.…”

Section: Introductionmentioning

confidence: 99%

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Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Yan

et al. 2015

J Assist Reprod Genet

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Purpose The study aims to elucidate the changes in testicular spermatogenic function in high-fat diet (HFD)-induced obese rats and to evaluate the protective effects of metformin intervention. Methods Male Sprague-Dawley rats (n=18) were randomly divided into a control group (standard diet), an HFD group, and a metformin group (HFD + metformin at 100 mg/kg, once daily by oral gavage). After 8 weeks, rats were euthanized, and the weights of body and testes were measured. Testis and epididymis were dissected and hematoxylin-eosin-stained for histopathological examination and semen parameter analysis. Blood samples were collected for assessment of sex hormones and metabolic parameters (serum glucose, insulin, and leptin). Spermatogenic cell apoptosis was accessed by TUNEL. Results Compared with the control group, the final body weight and weight gain were significantly higher in HFD rats, while the testicle weight and coefficients were lower. In HFD rats, metformin treatment induced weight loss and increased testicle weight (P<0.05). In HFD rats, obvious pathological changes in the testicular tissue were characterized by small, atrophic, and distorted seminiferous tubules and destroyed basement membrane. Metformin treatment protected against the HFD-induced decrease in the number of spermatogonia, Sertoli cells, and Leydig cells (P<0.05); ameliorated the HFD-induced increases in serum glucose, insulin, leptin, and estrogen; and decreased serum testosterone (P<0.05) and reduced the rate of testicular cell apoptosis in obese male rats. Finally, metformin significantly improved semen parameters (including concentration, viability, motility, and normal morphology) in HFD rats (P<0.05). Conclusions HFD-induced obesity in rats results in detrimental effects on spermatogenesis, semen quality, endogenous hormones, and testicular cell apoptosis. Metformin intervention improved the semen parameters, possibly due to its effects on weight loss, increased testicular weight, reduced testicular cell apoptosis, and resulted in restoration of hormonal homeostasis and correction of metabolic disorder.

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Section: Discussionmentioning

confidence: 96%

Section: Introductionmentioning

confidence: 99%

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Yan

et al. 2015

J Assist Reprod Genet

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“…Some suggested that metformin can induce hypothalamic leptin receptor expression and increase central leptin sensitivity which then inhibits food intake [17]. Others suggested that changed gastrointestinal physiology and circadian rhythm by metformin could also affect food intake, fat oxidation and storage [18]. Diabetes was induced in Wistar rats and then administered with or without metformin (500 mg·kg -1 ·d -1 p.o.…”

Section: Effects Of Metformin On Glucose Insulin and Lipid Profilesmentioning

confidence: 99%

The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats

et al. 2017

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TYPE 2 DIABETES MELLITUS (T2DM) is associated with obesity and insulin resistance and has severe complications. As an effective and safe oral drug, metformin has been used to treat T2DM for almost fifty years. Possible mechanisms of metformin in improving glucose homeostasis are partially depended on the activation of adenosine monophosphate-activated protein kinase (AMPK) which then inhibits glucose output and increases insulin sensitivity in peripheral tissues [1].Fibroblast growth factor-19 (FGF19) and FGF21 belong to beta-klotho family, and recent studies showedThe effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats Yan Wang 1), 2) , Ningning Dang 3) , Pei Sun 2) , Jin Xia 2), 4) , Chunxue Zhang 2), 4) and Shuguang Pang 1), 2), 4) Abstract. To understand metformin's effects on fibroblast growth factors (FGFs) and fibroblast growth factor receptor 1 (FGFR1), we investigated circulating fibroblast growth factor-19 (FGF19), FGF21 levels, and FGFR1 in type 2 diabetes mellitus (T2DM). In addition, protein kinase B (Akt) signaling pathway was detected to explain the possible mechanisms. T2DM was induced by feeding rats with high-fat diet for 11 weeks, followed by a low dose of streptozotocin (STZ, 30-35 mg/kg, intraperitoneally). Control rats (Con) were fed on a normal chow; diabetic rats (DM) were fed on high-fat diet supplemented with or without metformin (METF) for 12 weeks (500 mg·kg -1 ·d -1 ). Biochemical parameters were detected at the end of 24th weeks. FGFR1 expression and protein kinase B (Akt) phosphorylation in the pancreas and visceral adipose tissues were detected using either Western blot (WB) or immunohistochemistry (IHC). Serum FGF19 and FGF21 were measured using enzyme-linked immune sorbent assay (ELISA). Metformin treated DM rats showed improved glucose, lipid and bile acid metabolism. Besides, significantly decreased FGF19 and increased FGF21 were observed in DM+METF rats. DM rats showed significantly increased FGFR1 both in the pancreas and visceral adipose tissues. While in DM+METF rats, FGFR1 was almost remained at a normal level in the pancreas and increased in the visceral adipose tissue compared to that in DM rats. Besides, metformin treatment restores Akt phosphorylation in both tissues. The altered glucose and lipid profiles by metformin treatment may be associated with the increased circulating FGF21 and tissue-specific expressions of FGFR1.Key words: Diabetes, FGF21, FGFR1, β cell, Visceral adipose that they were produced by the activation of Farnesoid X Receptor (FXR) in the ileum and liver, respectively [2,3]. FGF19 and FGF21 are emerging as endocrine hormones since they showed novel roles in bile acid, lipid, and glucose metabolism [4][5][6]. In obese or diabetic animal models, administration of FGF19 and FGF21 led to beneficial effects on metabolism through increasing insulin sensitivity, energy expenditure and white adipose browning [7][8][9][10].FGFs exert their roles by binding...

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“…The mechanisms by which metformin improves glycemic control is mainly by reducing hepatic glucose production, and to a lesser extent, via enhancing peripheral insulin sensitivity, blocking gastrointestinal glucose absorption, modulating gut microbiota and promoting incretin axis (Ikeda et al 2000, Green et al 2006, Maida et al 2011, Miller et al 2013, Foretz et al 2014, Madiraju et al 2014, Shin et al 2014. In addition to its antidiabetic effects, metformin demonstrates multiple beneficial 'side effects' such as antiobesity, antihepatosteatotic and anti-inflammatory effects, and is currently in clinical trials to treat obesity (Malin & Kashyap 2014), NAFLD (Zheng et al 2015), polycystic ovary syndrome (PCOS) (Misso & Teede 2015) and certain types of cancer (Leone et al 2014, Morales & Morris 2015. Emerging evidence suggests that enhanced leptin sensitivity may contribute to the weight-loss effect of this drug (Aubert et al 2011, Malin & Kashyap 2014.…”

Section: Introductionmentioning

confidence: 99%

Metformin increases hepatic leptin receptor and decreases steatosis in mice

Tang

Xiang

et al. 2016

Journal of Endocrinology

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In addition to the ascertained efficacy as antidiabetic drug, metformin is increasingly being used as weight-loss agent in obesity, and as insulin sensitizer in nonalcoholic fatty liver disease (NAFLD). However, the mechanisms underlying these effects are still incompletely understood. Emerging evidence suggest metformin as leptin sensitizer to mediate the weight-loss effect in the brain. In this study, we investigated effects of metformin on expression of leptin receptors in liver and kidney in mice. C57BL/6 mice were fed with chow diet (CD) or high-fat diet (HF) for 5 months. Afterward, mice were treated with metformin (50 mg/kg or 200 mg/kg) for 15 days. Metabolic parameters and hepatic gene expression were analyzed at the end of the treatment. We also tested the effects of metformin on plasma-soluble leptin receptor (sOB-R) levels in newly diagnosed type 2 diabetes mellitus (T2DM) patients, and assessed its effect on hepatosteatosis in mice. Results showed that metformin upregulates the expression of leptin receptors (OB-Ra, -Rb, -Rc, and -Rd) in liver but not kidney. The stimulation effect is dosedependent in both chow and HF mice. Upregulation of OB-Rb, long signaling isoform, needs a relatively higher dose of metformin. This effect was paralleled by increased sOBR levels in mice and T2DM patients, and decreased hepatic triglyceride (TG) content and lipogenic gene expression, including sterol regulatory element-binding protein 1c (SREBP-1c), fatty acid synthase (FAS) and acetyl-CoA carboxylase-1 (ACC-1). Taken together, these data identify hepatic leptin receptor as target gene being upregulated by metformin which may enhance leptin sensitivity in liver to alleviate steatosis.

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Effects of metformin on weight loss

Cited by 205 publications

References 43 publications

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

Protective effects of metformin on reproductive function in obese male rats induced by high-fat diet

The effects of metformin on fibroblast growth factor 19, 21 and fibroblast growth factor receptor 1 in high-fat diet and streptozotocin induced diabetic rats

Metformin increases hepatic leptin receptor and decreases steatosis in mice

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