scholarly journals Modulation of Gr1low monocyte subset impacts insulin sensitivity and weight gain upon high-fat diet in female mice

2017 ◽  
Vol 41 (12) ◽  
pp. 1805-1814 ◽  
Author(s):  
S Béliard ◽  
W Le Goff ◽  
F Saint-Charles ◽  
L Poupel ◽  
V Deswaerte ◽  
...  
Keyword(s):  
Weight Gain ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Monocyte Subset ◽  
High Fat ◽  
Female Mice

scholarly journals Tpcn2 knockout mice have improved insulin sensitivity and are protected against high-fat diet-induced weight gain

2018 ◽  
Vol 50 (8) ◽  
pp. 605-614
Author(s):  
Hong He ◽  
Katie Holl ◽  
Sarah DeBehnke ◽  
Chay Teng Yeo ◽  
Polly Hansen ◽  
...  
Keyword(s):  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Knockout Mice ◽  
High Fat Diet ◽  
Wild Type ◽  
High Fat ◽  
Male And Female ◽  
Female Mice

Type 2 diabetes is a complex disorder affected by multiple genes and the environment. Our laboratory has shown that in response to a glucose challenge, two-pore channel 2 ( Tpcn2) knockout mice exhibit a decreased insulin response but normal glucose clearance, suggesting they have improved insulin sensitivity compared with wild-type mice. We tested the hypothesis that improved insulin sensitivity in Tpcn2 knockout mice would protect against the negative effects of a high fat diet. Male and female Tpcn2 knockout (KO), heterozygous (Het), and wild-type (WT) mice were fed a low-fat (LF) or high-fat (HF) diet for 24 wk. HF diet significantly increases body weight in WT mice relative to those on the LF diet; this HF diet-induced increase in body weight is blunted in the Het and KO mice. Despite the protection against diet-induced weight gain, however, Tpcn2 KO mice are not protected against HF-diet-induced changes in glucose or insulin area under the curve during glucose tolerance tests in female mice, while HF diet has no significant effect on glucose tolerance in the male mice, regardless of genotype. Glucose disappearance during an insulin tolerance test is augmented in male KO mice, consistent with our previous findings suggesting enhanced insulin sensitivity in these mice. Male KO mice exhibit increased fasting plasma total cholesterol and triglyceride concentrations relative to WT mice on the LF diet, but this difference disappears in HF diet-fed mice where there is increased cholesterol and triglycerides across all genotypes. These data demonstrate that knockout of Tpcn2 may increase insulin action in male, but not female, mice. In addition, both male and female KO mice are protected against diet-induced weight gain, but this protection is likely independent from glucose tolerance, insulin sensitivity, and plasma lipid levels.

scholarly journals Partial Deficiency of Zfp217 Resists High-Fat Diet-Induced Obesity by Increasing Energy Metabolism in Mice

2021 ◽  
Vol 22 (10) ◽  
pp. 5390
Author(s):  
Qianhui Zeng ◽  
Nannan Wang ◽  
Yaru Zhang ◽  
Yuxuan Yang ◽  
Shuangshuang Li ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Metabolism ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Chow Diet ◽  
High Fat ◽  
Glycolipid Metabolism ◽  
Partial Deficiency

Obesity-induced adipose tissue dysfunction and disorders of glycolipid metabolism have become a worldwide research priority. Zfp217 plays a crucial role in adipogenesis of 3T3-L1 preadipocytes, but about its functions in animal models are not yet clear. To explore the role of Zfp217 in high-fat diet (HFD)-induced obese mice, global Zfp217 heterozygous knockout (Zfp217+/−) mice were constructed. Zfp217+/− mice and Zfp217+/+ mice fed a normal chow diet (NC) did not differ significantly in weight gain, percent body fat mass, glucose tolerance, or insulin sensitivity. When challenged with HFD, Zfp217+/− mice had less weight gain than Zfp217+/+ mice. Histological observations revealed that Zfp217+/− mice fed a high-fat diet had much smaller white adipocytes in inguinal white adipose tissue (iWAT). Zfp217+/− mice had improved metabolic profiles, including improved glucose tolerance, enhanced insulin sensitivity, and increased energy expenditure compared to the Zfp217+/+ mice under HFD. We found that adipogenesis-related genes were increased and metabolic thermogenesis-related genes were decreased in the iWAT of HFD-fed Zfp217+/+ mice compared to Zfp217+/− mice. In addition, adipogenesis was markedly reduced in mouse embryonic fibroblasts (MEFs) from Zfp217-deleted mice. Together, these data indicate that Zfp217 is a regulator of energy metabolism and it is likely to provide novel insight into treatment for obesity.

scholarly journals Tpcn2 Knock‐Out Mice Have Improved Insulin Sensitivity and Are Protected Against High‐Fat Diet Induced Weight Gain.

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Leah Solberg Woods ◽  
Katie Holl ◽  
Hong He ◽  
Sarah DeBehnke ◽  
Chay Teng Yeo ◽  
...  
Keyword(s):  
Weight Gain ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
High Fat ◽  
Knock Out ◽  
Knock Out Mice

Nobiletin Prevents High-Fat Diet-Induced Dysregulation of Intestinal Lipid Metabolism and Attenuates Postprandial Lipemia

2021 ◽  
Author(s):  
Nadya M. Morrow ◽  
Natasha A. Trzaskalski ◽  
Antonio A. Hanson ◽  
Evgenia Fadzeyeva ◽  
Dawn E. Telford ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Insulin Sensitivity ◽  
High Fat Diet ◽  
Postprandial Lipemia ◽  
Intestinal Morphology ◽  
High Fat ◽  
Male And Female ◽  
Female Mice ◽  
Triglyceride Accumulation ◽  
Phosphorylated Akt

Objective: Nobiletin is a dietary flavonoid that improves insulin resistance and atherosclerosis in mice with metabolic dysfunction. Dysregulation of intestinal lipoprotein metabolism contributes to atherogenesis. The objective of the study was to determine if nobiletin targets the intestine to improve metabolic dysregulation in both male and female mice. Approach and Results: Triglyceride-rich lipoprotein (TRL) secretion, intracellular triglyceride kinetics, and intestinal morphology were determined in male and female LDL (low-density lipoprotein) receptor knockout, and male wild-type mice fed a standard laboratory diet or high-fat, high-cholesterol diet ± nobiletin using an olive oil gavage, radiotracers, and electron microscopy. Nobiletin attenuated postprandial TRL levels in plasma and enhanced TRL clearance. Nobiletin reduced fasting jejunal triglyceride accumulation through accelerated TRL secretion and lower jejunal fatty acid synthesis with no impact on fatty acid oxidation. Fasting-refeeding experiments revealed that nobiletin led to higher levels of phosphorylated AKT and FoxO1 (forkhead box O1) and normal Srebf1-c expression indicating increased insulin sensitivity. Intestinal length and weight were diminished by high-fat feeding and restored by nobiletin. Both fasting and postprandial plasma GLP-1 (glucagon-like peptide-1; and likely GLP-2) were elevated in response to nobiletin. Treatment with a GLP-2 receptor antagonist, GLP-2(3-33), reduced villus length in high fat-fed mice but did not impact TRL secretion in any diet group. In contrast to males, nobiletin did not improve postprandial lipid parameters in female mice. Conclusions: Nobiletin opposed the effects of the high-fat diet by normalizing intestinal de novo lipogenesis through improved insulin sensitivity. Nobiletin prevents postprandial lipemia because the enhanced TRL clearance more than compensates for increased TRL secretion.

scholarly journals Anti-Obesity Effects of Tanshinone I from Salvia miltiorrhiza Bunge in Mice Fed a High-Fat Diet through Inhibition of Early Adipogenesis

Nutrients ◽  
2020 ◽  
Vol 12 (5) ◽  
pp. 1242
Author(s):  
Dae Young Jung ◽  
Ji-Hyun Kim ◽  
Myeong Ho Jung
Keyword(s):  
Cell Cycle ◽  
Body Weight ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Glucose Metabolism ◽  
High Fat Diet ◽  
Salvia Miltiorrhiza ◽  
Obese Mice ◽  
High Fat ◽  
Salvia Miltiorrhiza Bunge

Tanshinone I (Tan I) is a diterpenoid isolated from Salvia miltiorrhiza Bunge and exhibits antitumor effects in several cancers. However, the anti-obesity properties of Tan I remain unexplored. Here, we evaluated the anti-obesity effects of Tan I in high-fat-diet (HFD)-induced obese mice and investigated the underlying molecular mechanisms in 3T3-L1 cells. HFD-induced obese mice were orally administrated Tan I for eight weeks, and body weight, weight gain, hematoxylin and eosin staining and serum biological parameters were examined. The adipogenesis of 3T3-L1 preadipocytes was assessed using Oil Red O staining and measurement of intracellular triglyceride (TG) levels, and mitotic clonal expansion (MCE) and its related signal molecules were analyzed during early adipogenesis of 3T3-L1 cells. The administration of Tan I significantly reduced body weight, weight gain, and white adipocyte size, and improved obesity-induced serum levels of glucose, free fatty acid, total TG, and total cholesterol in vivo in HFD-induced obese mice. Furthermore, Tan I-administered mice demonstrated improvement of glucose metabolism and insulin sensitivity. Treatment with Tan I inhibited the adipogenesis of 3T3-L1 preadipocytes in vitro, with this inhibition mainly occurring at an early phase of adipogenesis through the attenuation of MCE via cell cycle arrest at the G1/S phase transition. Tan I inhibited the phosphorylation of p38, extracellular signal-regulated kinase (ERK), and Akt during the process of MCE, while it stimulated the phosphorylation of AMP-activated protein kinase. Furthermore, Tan I repressed the expression of CCAAT-enhancer-binding protein β (C/EBPβ), histone H3K9 demethylase JMJD2B, and subsequently cell cycle genes. Moreover, Tan I regulated the expression of early adipogenic transcription factors including GATAs and Kruppel-like factor family factors. These results indicate that Tan I prevents HFD-induced obesity via the inhibition of early adipogenesis, and thus improves glucose metabolism and insulin sensitivity. This suggests that Tan I possesses therapeutic potential for the treatment of obesity and obesity-related diseases.

scholarly journals Lemon Balm Extract ALS-L1023 Regulates Obesity and Improves Insulin Sensitivity via Activation of Hepatic PPARα in High-Fat Diet-Fed Obese C57BL/6J Mice

2020 ◽  
Vol 21 (12) ◽  
pp. 4256
Author(s):  
Dongju Lee ◽  
Yujin Shin ◽  
Jong Seong Roh ◽  
Jiwon Ahn ◽  
Sunhyo Jeoong ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Lipid Accumulation ◽  
High Fat Diet ◽  
Obese Mice ◽  
High Fat ◽  
Lemon Balm ◽  
Hepatic Lipid ◽  
Hepatic Lipid Accumulation

Our previous studies demonstrated that peroxisome proliferator-activated receptor α (PPARα) activation reduces weight gain and improves insulin sensitivity in obese mice. Since excess lipid accumulation in non-adipose tissues is suggested to be responsible for the development of insulin resistance, this study was undertaken to examine whether the lemon balm extract ALS-L1023 regulates hepatic lipid accumulation, obesity, and insulin resistance and to determine whether its mechanism of action involves PPARα. Administration of ALS-L1023 to high-fat-diet-induced obese mice caused reductions in body weight gain, visceral fat mass, and visceral adipocyte size without changes of food consumption profiles. ALS-L1023 improved hyperglycemia, hyperinsulinemia, glucose and insulin tolerance, and normalized insulin-positive β-cell area in obese mice. ALS-L1023 decreased hepatic lipid accumulation and concomitantly increased the expression of PPARα target genes responsible for fatty acid β-oxidation in livers. In accordance with the in vivo data, ALS-L1023 reduced lipid accumulation and stimulated PPARα reporter gene expression in HepG2 cells. These effects of ALS-L1023 were comparable to those of the PPARα ligand fenofibrate, while the PPARα antagonist GW6471 inhibited the actions of ALS-L1023 on lipid accumulation and PPARα luciferase activity in HepG2 cells. Higher phosphorylated protein kinase B (pAkt)/Akt ratios and lower expression of gluconeogenesis genes were observed in the livers of ALS-L1023-treated mice. These results indicate that ALS-L1023 may inhibit obesity and improve insulin sensitivity in part through inhibition of hepatic lipid accumulation via hepatic PPARα activation.

scholarly journals Inactivation of SPAK kinase reduces body weight gain in mice fed a high-fat diet by improving energy expenditure and insulin sensitivity

2018 ◽  
Vol 314 (1) ◽  
pp. E53-E65 ◽  
Author(s):  
Ivan Torre-Villalvazo ◽  
Luz Graciela Cervantes-Pérez ◽  
Lilia G. Noriega ◽  
Jose V. Jiménez ◽  
Norma Uribe ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Weight Gain ◽  
Insulin Sensitivity ◽  
Energy Expenditure ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Whole Body ◽  
High Fat ◽  
The Metabolic Syndrome ◽  
Brown Adipose

The STE20/SPS1-related proline-alanine-rich protein kinase (SPAK) controls the activity of the electroneutral cation-chloride cotransporters (SLC12 family) and thus physiological processes such as modulation of cell volume, intracellular chloride concentration [Cl−]i, and transepithelial salt transport. Modulation of SPAK kinase activity may have an impact on hypertension and obesity, as STK39, the gene encoding SPAK, has been suggested as a hypertension and obesity susceptibility gene. In fact, the absence of SPAK activity in mice in which the activating threonine in the T loop was substituted by alanine (SPAK-KI mice) is associated with decreased blood pressure; however its consequences in metabolism have not been explored. Here, we fed wild-type and homozygous SPAK-KI mice a high-fat diet for 17 wk to evaluate weight gain, circulating substrates and hormones, energy expenditure, glucose tolerance, and insulin sensitivity. SPAK-KI mice exhibit resistance to HFD-induced obesity and hepatic steatosis associated with increased energy expenditure, higher thermogenic activity in brown adipose tissue, increased mitochondrial activity in skeletal muscle, and reduced white adipose tissue hypertrophy mediated by augmented whole body insulin sensitivity and glucose tolerance. Our data reveal a previously unrecognized role for the SPAK kinase in the regulation of energy balance, thermogenesis, and insulin sensitivity, suggesting that this kinase could be a new drug target for the treatment of obesity and the metabolic syndrome.

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