A 24‐month metformin treatment study of children with obesity: Changes in circulating GDF ‐15 and associations with changes in body weight and visceral fat

2021 ◽  
Author(s):  
Gemma Carreras‐Badosa ◽  
Ariadna Gómez‐Vilarrubla ◽  
Berta Mas‐Parés ◽  
José‐María Martínez‐Calcerrada ◽  
Silvia Xargay‐Torrent ◽  
...  
Author(s):  
Nami Yamanaka ◽  
Shinichiro Saito ◽  
Kazuya Kozuma ◽  
Noriko Osaki ◽  
Yoshihisa Katsuragi

Circulation ◽  
2015 ◽  
Vol 132 (suppl_3) ◽  
Author(s):  
Soohyun Nam ◽  
Soohyun Nam ◽  
Devon A Dobrosielski ◽  
Kerry J Stewart

Background: Though a high amount of visceral fat is associated with insulin resistance, which can lead to type 2 diabetes (T2D) and cardiovascular diseases (CVDs), less is known about whether lifestyle modification (weight loss diet and exercise) induced changes in visceral fat are associated with improvements in glycemia. Methods: We randomized 77 individuals aged 35-65 years with T2D or pre-diabetes to 6-months of weight loss diet (D); or D combined with supervised moderate-intensity exercise training (D+E). Study measures were total abdominal, visceral and subcutaneous fat volumes by magnetic resonance imaging, aerobic fitness expressed as VO 2 peak during treadmill testing, body mass index (BMI), and HbA1c levels from blood samples. Results: Of 77 subjects (mean age, 54.8±7.8 years; mean BMI, 34.5 ± 4.7 kg/m 2 , women, 77.9%; Whites-65%, Blacks-34%, Asians-1%), n=37 had T2D and n=40 had pre-diabetes. At 6 months, both D and D+E groups improved from baseline (p<0.05 for all) but did not differ in their changes for body weight (D: -6.04 ± 4.54 kg; D+E: -6.68 ± 4.48 kg, p= 0.61 for the group differences in change), abdominal total fat (D: -101.93 ± 68.67 cm 2 ; D+E:-104.16 ± 72.37 cm 2 , p= 0.92), visceral fat (D:-25.53 ± 39.44 cm 2 ; D+E:,-23.24 ± 35.62 cm 2 , p=0.85), HbA1c (D:0.04 ± 0.46%; D+E:0.03 ± 0.63%, p=0.96), and VO 2 peak (D: 2.26 ± 3.92 ml/kg/min ; D+E:3.71 ± 2.65 ml/kg/min, p=0.11). In a multivariate analysis, adjusting for baseline visceral fat, T2D status, body weight loss and increases in aerobic fitness, a reduction in HbA1c (β=-0.49, p =0.007) was associated with a reduction in visceral fat (R 2 =0.34, p=0.02). Conclusion: The key finding was that diet or diet plus exercise-mediated reductions in visceral fat was associated with reduced HbA1c among individuals with T2D or pre-diabetes. These data contribute to growing body of evidence of the benefits of reducing abdominal obesity, in this case, resulting in better glycemic control in T2D and pre-diabetes.


2020 ◽  
Author(s):  
Clayton Spada ◽  
Chau Vu ◽  
Iona Raymond ◽  
Warren Tong ◽  
Chia-Lin Chuang ◽  
...  

Abstract Background Bimatoprost negatively regulates adipogenesis in vitro and likely participates in a negative feedback loop on anandamide-induced adipogenesis. Here, we investigate the broader metabolic effects of bimatoprost action in vivo in rats under both normal state and obesity-inducing conditions. Methods Male Sprague Dawley rats were a fed standard chow (SC) diet in conjunction with dermally applied bimatoprost treatment for a period of 9–10 weeks. Body weight gain, energy expenditure, food intake, and hormones associated with satiety were measured. Gastric emptying was also separately evaluated. In obesity-promoting diet studies, rats were fed a cafeteria diet (CAF) and gross weight, fat accumulation in SQ, visceral fat and liver was evaluated together with standard serum chemistry. Results Chronic bimatoprost administration attenuated weight gain in rats fed either standard or obesity-promoting diets over a 9–10 weeks. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Additionally, SQ and visceral fat mass was distinctly affected by treatment. Bimatoprost increased satiety as measured by decreased food intake, gastric emptying and circulating gut hormone levels. Conclusions These findings suggest that bimatoprost (and possibly prostamide F2α) regulates energy homeostasis through actions on dietary intake. These actions likely counteract the metabolic actions of anandamide through the endocannabinoid system potentially revealing a new pathway that could be exploited for therapeutic development.


2019 ◽  
Vol 40 (41) ◽  
pp. 3409-3417 ◽  
Author(s):  
Mohapradeep Mohan ◽  
Shaween Al-Talabany ◽  
Angela McKinnie ◽  
Ify R Mordi ◽  
Jagdeep S S Singh ◽  
...  

Abstract Aim We tested the hypothesis that metformin may regress left ventricular hypertrophy (LVH) in patients who have coronary artery disease (CAD), with insulin resistance (IR) and/or pre-diabetes. Methods and results We randomly assigned 68 patients (mean age 65 ± 8 years) without diabetes who have CAD with IR and/or pre-diabetes to receive either metformin XL (2000 mg daily dose) or placebo for 12 months. Primary endpoint was change in left ventricular mass indexed to height1.7 (LVMI), assessed by magnetic resonance imaging. In the modified intention-to-treat analysis (n = 63), metformin treatment significantly reduced LVMI compared with placebo group (absolute mean difference −1.37 (95% confidence interval: −2.63 to −0.12, P = 0.033). Metformin also significantly reduced other secondary study endpoints such as: LVM (P = 0.032), body weight (P = 0.001), subcutaneous adipose tissue (P = 0.024), office systolic blood pressure (BP, P = 0.022) and concentration of thiobarbituric acid reactive substances, a biomarker for oxidative stress (P = 0.04). The glycated haemoglobin A1C concentration and fasting IR index did not differ between study groups at the end of the study. Conclusion Metformin treatment significantly reduced LVMI, LVM, office systolic BP, body weight, and oxidative stress. Although LVH is a good surrogate marker of cardiovascular (CV) outcome, conclusive evidence for the cardio-protective role of metformin is required from large CV outcomes trials.


2014 ◽  
Vol 39 (12) ◽  
pp. 1373-1379 ◽  
Author(s):  
Hiranya Pintana ◽  
Jirapas Sripetchwandee ◽  
Luerat Supakul ◽  
Nattayaporn Apaijai ◽  
Nipon Chattipakorn ◽  
...  

Oxidative stress in the obese-insulin resistant condition has been shown to affect cognitive as well as brain mitochondrial functions. Garlic extract has exerted a potent antioxidant effect. However, the effects of garlic extract on the brain of obese-insulin resistant rats have never been investigated. We hypothesized that garlic extract improves cognitive function and brain mitochondrial function in obese-insulin resistant rats induced by long-term high-fat diet (HFD) consumption. Male Wistar rats were fed either normal diet or HFD for 16 weeks (n = 24/group). At week 12, rats in each dietary group received either vehicle or garlic extract (250 and 500 mg·kg–1·day–1) for 28 days. Learning and memory behaviors, metabolic parameters, and brain mitochondrial function were determined at the end of treatment. HFD led to increased body weight, visceral fat, plasma insulin, cholesterol, and malondialdehyde (MDA) levels, indicating the development of insulin resistance. Furthermore, HFD rats had cognitive deficit and brain mitochondrial dysfunction. HFD rats treated with both doses of garlic extract had decreased body weight, visceral fat, plasma cholesterol, and MDA levels. Garlic extract also improved cognitive function and brain mitochondrial function, which were impaired in obese-insulin resistant rats caused by HFD consumption.


2008 ◽  
Vol 93 (5) ◽  
pp. 1841-1845 ◽  
Author(s):  
Lourdes Ibáñez ◽  
Abel López-Bermejo ◽  
Marta Díaz ◽  
Maria Victoria Marcos ◽  
Francis de Zegher

Abstract Context and Objective: A low birth weight (LBW) tends to be followed by overweight due to an excess of fat, including visceral fat. LBW girls with precocious pubarche (PP) (pubic hair &lt; 8 yr) are at high risk for developing an adipose state of hyperinsulinemic androgen excess that leads toward early menarche. We explored the effects of insulin sensitization with metformin in LBW-PP girls. Setting, Design, Patients, Intervention: Prepubertal LBW girls with PP (mean body weight 2.4 kg; age 7.9 yr; body mass index 18.4 kg/m2) were studied. Girls were randomly assigned to remain untreated (n=19) or receive metformin for 4 yr (n = 19; 425 mg/d for 2 yr, then 850 mg/d for 2 yr). Main Outcomes: At the start and after 4 yr, height, weight, fasting insulin, glucose, IGF-I, testosterone, lipids, leptin, high molecular weight adiponectin, body composition by absorptiometry, abdominal fat partitioning (only 4 yr) by magnetic resonance imaging, and menarcheal status were determined. Results: Metformin-treated girls gained on average 5.5 kg (or ∼50%) less fat, after 4 yr were less insulin resistant and less hyperandrogenic, had lower IGF-I levels and a less atherogenic lipid profile, and were less likely to be post-menarcheal than untreated girls, whereas their gain in height, lean mass, and bone mineral density were similar. After 4 yr, untreated girls had more visceral fat, a higher ratio of visceral-to-sc fat, and a higher leptin-to-high molecular weight adiponectin ratio (all ∼50% higher) than metformin-treated girls. Conclusion: Long-term metformin treatment appears to reduce total and visceral fat in LBW-PP girls, and to delay menarche without attenuating linear growth, thereby opening the perspective that adult height may be increased.


Health ◽  
2011 ◽  
Vol 03 (02) ◽  
pp. 73-76 ◽  
Author(s):  
Da-Hong Wang ◽  
Nobuyuki Miyatake ◽  
Michiko Kogashiwa ◽  
Takeyuki Numata ◽  
Keiki Ogino

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Kehinde Samuel Olaniyi ◽  
Morounkeji Nicole Owolabi ◽  
Chukwubueze Lucky Atuma ◽  
Toluwani Bosede Agunbiade ◽  
Bolanle Yemisi Alabi

AbstractWe investigated the hypothesis that acetate ameliorates brain-adipose metabolic dysfunction (BAMED) in high fat diet (HFD)-induced obesity, possibly by modulation of peroxisome proliferator-activated receptor-γ (PPAR-γ). Ten-week-old male Wistar rats were randomly assigned into four groups (n = 6/group): Control, acetate and obese with or without acetate groups received vehicle (distilled water; po), acetate (200 mg/kg, po) and 40% HFD with or without acetate respectively. The treatments lasted for 12 weeks. Obese animals showed increase in body weight, visceral fat mass, insulin and triglyceride-glucose index and a reduction in insulin sensitivity. In addition, obese animals also showed increase in plasma/hypothalamic and adipose pyruvate dehydrogenase kinase-4, lactate-pyruvate ratio, malondialdehyde, γ-glutamyl transferase, and a decrease in glucose-6-phosphate dehydrogenase, glutathione, nitric oxide and PPAR-γ. HFD also elevated plasma/hypothalamic lipid and decreased adipose lipid profile, increased hypothalamic and adipose tumor necrosis factor-α, interleukin-6 and histone deacetylase (HDAC), and elevated plasma/adipose leptin. These alterations were reversed by concomitant administration of acetate. The present results demonstrate that obesity is characterized by BAMED, which is accompanied by altered HDAC/PPAR-γ. The results in addition suggest that acetate, an HDAC inhibitor rescues BAMED with consequent normalization of body weight and visceral fat mass by modulation of PPAR-γ and suppression of oxidative stress.


2014 ◽  
Vol 11 (1) ◽  
pp. 42-47
Author(s):  
M I Fadeeva ◽  
L V Savelieva

Hyperinsulinism and insulin resistance, hypogonadism in men and women are often associated with obesity and may be its consequences and to be a primary preceding the development of overweight. A characteristic feature of the endocrine obesity is an increase in body weight due to visceral fat with redistribution on central type, accompanied by the development of the metabolic and endocrine disorders. Mechanisms of obesity in various hormonal disturbances are different. In general in the vast majority approaches of obesity treatment do not differ from generally accepted. Adequate correction of hormonal disorders can reduce body weight and contribute to the improvement of endocrine-metabolic parameters.


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