scholarly journals Regulation of glucose metabolism via hepatic forkhead transcription factor 1 (FoxO1) by Morinda citrifolia (noni) in high-fat diet-induced obese mice

2011 ◽  
Vol 108 (2) ◽  
pp. 218-228 ◽  
Author(s):  
Pratibha V. Nerurkar ◽  
Adrienne Nishioka ◽  
Philip O. Eck ◽  
Lisa M. Johns ◽  
Esther Volper ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Mrna Expression ◽  
High Fat Diet ◽  
Glucose Production ◽  
Analysis Data ◽  
Morinda Citrifolia ◽  
High Fat ◽  
Forkhead Transcription Factor ◽  
Human Hepatoma Cells ◽  
Insulin Tolerance

Renewed interest in alternative medicine among diabetic individuals prompted us to investigate anti-diabetic effects of Morinda citrifolia (noni) in high-fat diet (HFD)-fed mice. Type 2 diabetes is associated with increased glucose production due to the inability of insulin to suppress hepatic gluconeogenesis and promote glycolysis. Insulin inhibits gluconeogenesis by modulating transcription factors such as forkhead box O (FoxO1). Based on microarray analysis data, we tested the hypothesis that fermented noni fruit juice (fNJ) improves glucose metabolism via FoxO1 phosphorylation. C57BL/6 male mice were fed a HFD and fNJ for 12 weeks. Body weights and food intake were monitored daily. FoxO1 expression was analysed by real-time PCR and Western blotting. Specificity of fNJ-associated FoxO1 regulation of gluconeogenesis was confirmed by small interfering RNA (siRNA) studies using human hepatoma cells, HepG2. Supplementation with fNJ inhibited weight gain and improved glucose and insulin tolerance and fasting glucose in HFD-fed mice. Hypoglycaemic properties of fNJ were associated with the inhibition of hepatic FoxO1 mRNA expression, with a concomitant increase in FoxO1 phosphorylation and nuclear expulsion of the proteins. Gluconeogenic genes, phosphoenolpyruvate C kinase (PEPCK) and glucose-6-phosphatase (G6P), were significantly inhibited in mice fed a HFD+fNJ. HepG2 cells demonstrated more than 80 % inhibition of PEPCK and G6P mRNA expression in cells treated with FoxO1 siRNA and fNJ. These data suggest that fNJ improves glucose metabolism via FoxO1 regulation in HFD-fed mice.

scholarly journals Effect of Forskolin on Body Weight, Glucose Metabolism and Adipocyte Size of Diet-Induced Obesity in Mice

Animals ◽  
2021 ◽  
Vol 11 (3) ◽  
pp. 645
Author(s):  
Jing-Yi Chen ◽  
Shao-Yu Peng ◽  
Yeong-Hsiang Cheng ◽  
I-Ta Lee ◽  
Yu-Hsiang Yu
Keyword(s):  
Body Weight ◽  
Glucose Metabolism ◽  
Dimethyl Sulfoxide ◽  
High Fat Diet ◽  
Tolerance Test ◽  
Cell Diameter ◽  
High Fat ◽  
Fat Cell ◽  
Glucose Levels ◽  
Insulin Tolerance

The purpose of this study was to investigate the effects of forskolin on body weight, glucose metabolism and fat cell diameter in high-fat diet-induced obese mice. Four-week-old male mice (C57BL/6) were randomly assigned to 1 of 3 treatment groups: a high-fat diet plus 5% dimethyl sulfoxide (vehicle), high-fat diet plus 2 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide) and high-fat diet plus 4 mg/kg of forskolin (dissolved in 5% dimethyl sulfoxide). Forskolin or dimethyl sulfoxide was administered intraperitoneally every two days. The results indicated that no significant difference was observed in the body weight, feed intake and serum lipid parameters among groups at 20 weeks of age. The blood glucose levels were significantly reduced in the groups treated with 2 mg/kg of forskolin before glucose tolerance test. Forskolin administration linearly decreased blood glucose levels of high-fat diet-fed mice at 90 min and total area under curve (AUC) after insulin tolerance test. The subcutaneous adipocyte diameter was significantly reduced in the groups treated with 2 mg/kg of forskolin. Forskolin administration linearly reduced the gonadal adipocyte diameter of high-fat diet-fed mice. Forskolin significantly reduced the differentiation of murine mesenchymal stem cells into adipocytes and this was accompanied by a decrease in intracellular triglyceride content and an increase in glycerol concentration in the culture medium. The subcutaneous adipocyte diameter, gonadal adipocyte diameter and total AUC of insulin tolerance test were moderately negatively correlated with the concentration of forskolin in the high-fat diet-induced obese model. These results demonstrate that forskolin can regulate glucose metabolism and reduce fat cell diameter of high-fat diet-fed mice and inhibit the adipocyte differentiation of murine mesenchymal stem cells.

scholarly journals miR-22-3p is involved in gluconeogenic pathway modulated by 3,5-diiodo-L-thyronine (T2)

2019 ◽  
Vol 9 (1) ◽  
Author(s):  
Rosalba Senese ◽  
Federica Cioffi ◽  
Giuseppe Petito ◽  
Pieter de Lange ◽  
Aniello Russo ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
Glucose Homeostasis ◽  
High Fat Diet ◽  
Molecular Mechanisms ◽  
Metabolic Diseases ◽  
Tolerance Test ◽  
High Fat ◽  
Beneficial Effects ◽  
Insulin Tolerance

Abstract The 3,5-diiodo-L-thyronine (T2) has emerged as an active iodothyronine and its beneficial effects on glucose metabolism including glucose tolerance and insulin resistance is well established. However, little is known about its molecular mechanisms. Given the emerging importance of microRNAs in various metabolic diseases, in this study a possible link between the effects of T2 on glucose metabolism and miRNA expression was investigated by using an in vivo model in which T2 was administered in rats receiving a high fat diet, a condition known to impair glucose homeostasis. The results showed that T2-treated rats had a better tolerance to glucose load and a better performance at the insulin tolerance test in comparison to high fat diet animals. Interestingly, in the serum of the animals treated with T2 there was a general decrease of miRNAs with miR-22a-3p, miR-34c-5p and miR-33a-3p significantly downregulated. Furthermore, miR-22a-3p had the largest variation pointing toward its preeminent role in T2 metabolic effect. In fact, in liver there was an up-regulation of its target (Transcription Factor 7) Tcf7, which had an important impact on gluconeogenesis. This study provide, for the first time, evidences that miRNAs are involved in the effects exerted by T2 on glucose homeostasis.

scholarly journals Effects of Antarctic krill oil on lipid and glucose metabolism in C57BL/6J mice fed with high fat diet

2017 ◽  
Vol 16 (1) ◽  
Author(s):  
Dewei Sun ◽  
Liang Zhang ◽  
Hongjian Chen ◽  
Rong Feng ◽  
Peirang Cao ◽  
...  
Keyword(s):  
Glucose Metabolism ◽  
High Fat Diet ◽  
Antarctic Krill ◽  
Krill Oil ◽  
High Fat ◽  
Antarctic Krill Oil

scholarly journals The Irs1 Branch of the Insulin Signaling Cascade Plays a Dominant Role in Hepatic Nutrient Homeostasis

2009 ◽  
Vol 29 (18) ◽  
pp. 5070-5083 ◽  
Author(s):  
Shaodong Guo ◽  
Kyle D. Copps ◽  
Xiaocheng Dong ◽  
Sunmin Park ◽  
Zhiyong Cheng ◽  
...  
Keyword(s):  
Tyrosine Phosphorylation ◽  
High Fat Diet ◽  
Insulin Infusion ◽  
Dominant Role ◽  
Hepatic Glucose Production ◽  
Glucose Production ◽  
High Fat ◽  
Lipogenic Genes ◽  
Hepatic Glucose ◽  
Nutrient Homeostasis

ABSTRACT We used a Cre-loxP approach to generate mice with varied expression of hepatic Irs1 and Irs2 to establish the contribution of each protein to hepatic nutrient homeostasis. While nutrient-sensitive transcripts were expressed nearly normally in liver lacking Irs2 (LKO2 mice), these transcripts were significantly dysregulated in liver lacking Irs1 (LKO1 mice) or Irs1 and Irs2 together (DKO mice). Similarly, a set of key gluconeogenic and lipogenic genes was regulated nearly normally by feeding in liver retaining a single Irs1 allele without Irs2 (DKO/1 mice) but was poorly regulated in liver retaining one Irs2 allele without Irs1 (DKO/2 mice). DKO/2 mice, but not DKO/1 mice, also showed impaired glucose tolerance and insulin sensitivity—though both Irs1 and Irs2 were required to suppress hepatic glucose production during hyperinsulinemic-euglycemic clamp. In contrast, either hepatic Irs1 or Irs2 mediated suppression of HGP by intracerebroventricular insulin infusion. After 12 weeks on a high-fat diet, postprandial tyrosine phosphorylation of Irs1 increased in livers of control and LKO2 mice, whereas tyrosine phosphorylation of Irs2 decreased in control and LKO1 mice. Moreover, LKO1 mice—but not LKO2 mice—that were fed a high-fat diet developed postprandial hyperglycemia. We conclude that Irs1 is the principal mediator of hepatic insulin action that maintains glucose homeostasis.

Effect of High-Fat Diet on Glucose Metabolism in Selenocysteine Lyase Knockout Mouse

2011 ◽  
pp. P3-371-P3-371
Author(s):  
Lucia A Seale ◽  
Ann C Hashimoto ◽  
Christy L Gilman ◽  
Ali Seyedali ◽  
Marla J Berry
Keyword(s):  
Glucose Metabolism ◽  
High Fat Diet ◽  
Knockout Mouse ◽  
High Fat ◽  
Selenocysteine Lyase

scholarly journals Early Overnutrition Results in Early-Onset Arcuate Leptin Resistance and Increased Sensitivity to High-Fat Diet

Endocrinology ◽  
2010 ◽  
Vol 151 (4) ◽  
pp. 1598-1610 ◽  
Author(s):  
Maria M. Glavas ◽  
Melissa A. Kirigiti ◽  
Xiao Q. Xiao ◽  
Pablo J. Enriori ◽  
Sarah K. Fisher ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Body Weight ◽  
High Fat Diet ◽  
Arcuate Nucleus ◽  
Leptin Resistance ◽  
Signal Transducer ◽  
High Fat ◽  
Insulin Tolerance ◽  
Obesity And Diabetes ◽  
Transcription 3

Childhood obesity increases the risk of adult obesity and diabetes, suggesting that early overnutrition permanently programs altered energy and glucose homeostasis. In the present studies, we used a mouse model to investigate whether early overnutrition increases susceptibility to obesity and insulin resistance in response to a high-fat diet (HFD). Litters from Swiss Webster dams were culled to three [chronic postnatal overnutrition (CPO)] or 10 (control) pups and then weaned onto standard chow at postnatal day (P) 23. At 6 wk of age, a subset of mice was placed on HFD, and glucose and insulin tolerance were examined at 16–17 wk of age. Leptin sensitivity was determined by hypothalamic phosphorylated signal transducer and activator of transcription-3 immunoreactivity at P16 and adulthood after ip leptin. CPO mice exhibited accelerated body weight gain and hyperleptinemia during the preweaning period but only a slightly heavier body weight and normal glucose tolerance in adulthood on standard chow diet. Importantly, CPO mice exhibited significant leptin resistance in the arcuate nucleus, demonstrated by reduced activation of phospho-signal transducer and activator of transcription-3, as early as P16 and throughout life, despite normalized leptin levels. In response to HFD, CPO but not control mice displayed insulin resistance in response to an insulin tolerance test. In conclusion, CPO mice exhibited early and persistent leptin resistance in the arcuate nucleus and, in response to HFD, rapid development of obesity and insulin resistance. These studies suggest that early overnutrition can permanently alter energy homeostasis and significantly increase susceptibility to obesity and insulin resistance.

α1-Antitrypsin A treatment attenuates neutrophil elastase accumulation and enhances insulin sensitivity in adipose tissue of mice fed a high-fat diet.

2021 ◽  
Author(s):  
Randall F. D'Souza ◽  
Stewart W.C. Masson ◽  
Jonathan S. T. Woodhead ◽  
Samuel L James ◽  
Caitlin MacRae ◽  
...  
Keyword(s):  
Body Weight ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Glucose Uptake ◽  
Neutrophil Elastase ◽  
High Fat Diet ◽  
Tolerance Test ◽  
Metabolic Dysfunction ◽  
High Fat ◽  
Insulin Tolerance

Neutrophils accumulate in insulin sensitive tissues during obesity and may play a role in impairing insulin sensitivity. The major serine protease expressed by neutrophils is neutrophil elastase (NE), which is inhibited endogenously by α1-antitrypsin A (A1AT). We investigated the effect of exogenous (A1AT) treatment on diet induced metabolic dysfunction. Male C57Bl/6j mice fed a chow or a high fat diet (HFD) were randomized to receive 3x weekly i.p injections of either Prolastin (human A1AT; 2mg) or vehicle (PBS) for 10 weeks. Prolastin treatment did not affect plasma NE concentration, body weight, glucose tolerance or insulin sensitivity in chow fed mice. In contrast, Prolastin treatment attenuated HFD induced increases in plasma and white adipose tissue (WAT) NE without affecting circulatory neutrophil levels or increases in body weight. Prolastin-treated mice fed a HFD had improved insulin sensitivity, as assessed by insulin tolerance test, and this was associated with higher insulin-dependent IRS-1 (insulin receptor substrate) and AktSer473phosphorylation, and reduced inflammation markers in WAT but not liver or muscle. In 3T3-L1 adipocytes, Prolastin reversed recombinant NE-induced impairment of insulin-stimulated glucose uptake and IRS-1 phosphorylation. Furthermore, PDGF mediated p-AktSer473 activation and glucose uptake (which is independent of IRS-1) was not affected by recombinant NE treatment. Collectively, our findings suggest that NE infiltration of WAT during metabolic overload contributes to insulin-resistance by impairing insulin-induced IRS-1 signaling.

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