Treatment with constitutive androstane receptor ligand during pregnancy prevents insulin resistance in offspring from high-fat diet-induced obese pregnant mice

The constitutive androstane receptor (CAR) has been reported to decrease insulin resistance even during pregnancy, while exposure to a high-fat diet (HFD) in utero in mice can induce a type 2 diabetes phenotype that can be transmitted to the progeny. Therefore, we examined whether treatment with a CAR ligand during pregnancy could prevent hypertension, insulin resistance, and hyperlipidemia in the offspring from HFD-induced obese pregnant mice (OH mice). We employed four groups of offspring from HFD-fed and control diet-fed pregnant mice with or without treatment with a CAR ligand. Treatment with a CAR ligand during pregnancy improved glucose tolerance and the levels of triglyceride and adipocytokine and restored the changes induced by HFD with amelioration of hypertension in the adult OH mice. This treatment also increased adiponectin mRNA expression, suppressed leptin expression in adipose tissues of OH mice, and abolished the effect of HFD on the epigenetic modifications of the genes encoding adiponectin and leptin in the offspring during immaturity and adulthood. Our data suggest that CAR might be a potential therapeutic target to prevent metabolic syndrome in adulthood of offspring exposed to an HFD in utero.

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FGF15/FGF19 alleviates insulin resistance and upregulates placental IRS1/GLUT expression in pregnant mice fed a high-fat diet

Placenta ◽

10.1016/j.placenta.2021.07.286 ◽

2021 ◽

Author(s):

Shanshan Zhao ◽

Dongyu Wang ◽

Zhuyu Li ◽

Shuqia Xu ◽

Haitian Chen ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

High Fat ◽

Pregnant Mice ◽

Glut Expression

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In utero Exposure to Germinated Brown Rice and Its GABA Extract Attenuates High-Fat-Diet-Induced Insulin Resistance in Rat Offspring

Journal of Nutrigenetics and Nutrigenomics ◽

10.1159/000469663 ◽

2017 ◽

Vol 10 (1-2) ◽

pp. 19-31 ◽

Cited By ~ 1

Author(s):

Hadiza Altine Adamu ◽

Mustapha Umar Imam ◽

Ooi Der-Jiun ◽

Maznah Ismail

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Brown Rice ◽

In Utero ◽

In Utero Exposure ◽

High Fat ◽

Germinated Brown Rice ◽

Rat Offspring

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Treatment with a constitutive androstane receptor ligand ameliorates the signs of preeclampsia in high-fat diet-induced obese pregnant mice

Molecular and Cellular Endocrinology ◽

10.1016/j.mce.2011.07.047 ◽

2012 ◽

Vol 348 (1) ◽

pp. 120-127 ◽

Cited By ~ 18

Author(s):

H. Masuyama ◽

Y. Hiramatsu

Keyword(s):

High Fat Diet ◽

Constitutive Androstane Receptor ◽

High Fat ◽

Receptor Ligand ◽

Pregnant Mice

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Selenoprotein W deficiency does not affect oxidative stress and insulin sensitivity in the skeletal muscle of high-fat diet-fed obese mice

AJP Cell Physiology ◽

10.1152/ajpcell.00064.2019 ◽

2019 ◽

Vol 317 (6) ◽

pp. C1172-C1182 ◽

Cited By ~ 3

Author(s):

Min-Gyeong Shin ◽

Hye-Na Cha ◽

Soyoung Park ◽

Yong-Woon Kim ◽

Jong-Yeon Kim ◽

...

Keyword(s):

Oxidative Stress ◽

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

High Fat Diet ◽

Control Diet ◽

In Vivo Studies ◽

Selenoprotein W ◽

Obese Mice ◽

High Fat

Selenoprotein W (SelW) is a selenium-containing protein with a redox motif found abundantly in the skeletal muscle of rodents. Previous in vitro studies suggest that SelW plays an antioxidant role; however, relatively few in vivo studies have addressed the antioxidant role of SelW. Since oxidative stress is a causative factor for the development of insulin resistance in obese subjects, we hypothesized that if SelW plays a role as an antioxidant, SelW deficiency could aggravate the oxidative stress and insulin resistance caused by a high-fat diet. SelW deficiency did not affect insulin sensitivity and H2O2 levels in the skeletal muscle of control diet-fed mice. SelW levels in the skeletal muscle were decreased by high-fat diet feeding for 12 wk. High-fat diet induced obesity and insulin resistance and increased the levels of H2O2 and oxidative stress makers, which were not affected by SelW deficiency. High-fat diet feeding increased the expression of antioxidant enzymes; however, SelW deficiency did not affect the expression levels of antioxidants. These results suggest that SelW does not play a protective role against oxidative stress and insulin resistance in the skeletal muscle of high-fat diet-fed obese mice.

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Hypertension and sympathetic hyperactivity induced in rats by high-fat or glucose diets

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1991.260.1.e95 ◽

1991 ◽

Vol 260 (1) ◽

pp. E95-E100 ◽

Cited By ~ 5

Author(s):

L. N. Kaufman ◽

M. M. Peterson ◽

S. M. Smith

Keyword(s):

Dietary Fat ◽

High Fat Diet ◽

Control Diet ◽

Sprague Dawley ◽

High Fat ◽

Hypertensive Rats ◽

Diet Treatment ◽

Sprague Dawley Rats ◽

Sympathetic Nervous ◽

And Control

Male Sprague-Dawley rats fed either a high-fat diet or a glucose-enriched diet developed higher blood pressure (BP) than rats fed a control diet. After 8 wk of diet treatment systolic BP was 11% higher (P less than 0.01) in fat-fed rats and 7% higher (P less than 0.05) in glucose-fed rats when compared with rats fed the control diet. Rats fed the high-fat diet developed hypertension only when they were allowed to overeat and become obese and hyperinsulinemic. But when their feeding was restricted to prevent obesity and hyperinsulinemia, they remained normotensive. In contrast, elevated BP developed in rats consuming the glucose diet in the absence of obesity or hyperinsulinemia. After 7 wk of diet treatment, urinary norepinephrine excretion was 1.9 +/- 0.1, 1.9 +/- 0.1, and 1.5 +/- 0.1 micrograms/day in rats fed the high-fat, glucose, and control diets, respectively (P less than 0.05 vs. control). Higher norepinephrine excretion in hypertensive rats suggests that increased sympathetic nervous system (SNS) activity might participate in mediating the effects of dietary fat or glucose on BP. In addition, insulin may contribute to raising BP in rats fed the high-fat diet, either directly or indirectly through its stimulatory effect on the SNS. We conclude that chronic feeding of diets high in fat or glucose increases BP and enhances SNS activity in rats.

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260. Effects of diet-induced obesity on ovarian function and female fertility

Reproduction Fertility and Development ◽

10.1071/srb05abs260 ◽

2005 ◽

Vol 17 (9) ◽

pp. 105 ◽

Cited By ~ 1

Author(s):

C. E. Minge ◽

B. D. Bennett ◽

V. Tsagareli ◽

R. J. Norman ◽

M. Lane ◽

...

Keyword(s):

Insulin Resistance ◽

Glucose Tolerance ◽

High Fat Diet ◽

Ovarian Function ◽

Control Diet ◽

Female Fertility ◽

Ovulation Rate ◽

High Fat ◽

Blastocyst Development ◽

Diet Induced Obesity

Obesity and its related complications (metabolic syndrome, Type II diabetes and polycystic ovary syndrome) are increasingly associated with female infertility. Our research is focused on understanding how diet-induced obesity, which triggers insulin resistance and symptoms of chronic inflammation, directly impacts ovarian function and female fertility. Female mice were maintained on a “Western style” diet (22% fat, 0.15% cholesterol) or a matched control diet. Body weights were monitored weekly and after 16 weeks fasting insulin levels and glucose tolerance were assessed. Mice were then paired with males and tissues collected on day 1 on pregnancy. Blood samples were taken to determine levels of progesterone, metabolites (glucose, HDL/LDL) and inflammatory cytokines. Tissue weights (fat pads, liver, kidney, spleen, pancreas, ovary and uterus) were recorded and the reproductive tissues were fixed for analysis of histology and gene expression. Zygotes were isolated from the oviduct, cultured in vitro and scored for on-time development and differentially stained to assess blastocyst quality. Indices of ovarian function, including ovulation rate, steroid production and oocyte quality/blastocyst development will then be correlated with degrees of insulin resistance, dyslipidemia and inflammation. Five strains of mice were tested (CBA, Balb/c, C57, SV129 and Swiss) and showed significant differences in susceptibility to diet-induced obesity and insulin resistance. In CBA mice, the first group to be completed, the high fat diet significantly increased body weight, but did not result in overtly impaired glucose tolerance. The number of days to mating was slightly extended compared to mice on the control diet. Interestingly, the high fat diet did not affect ovulation rate but resulted in dramatically impaired blastocyst development. The results of this study will reveal how ovarian folliculogenesis, oocyte competence and ovulation are affected by obesity-induced metabolic changes, which are increasingly affecting women of reproductive age.

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The Effects of Duodenojejunal Omega Switch in Combination with High-Fat Diet and Control Diet on Incretins, Body Weight, and Glucose Tolerance in Sprague-Dawley Rats

Obesity Surgery ◽

10.1007/s11695-017-2883-3 ◽

2017 ◽

Vol 28 (3) ◽

pp. 748-759 ◽

Cited By ~ 10

Author(s):

Dominika Stygar ◽

Tomasz Sawczyn ◽

Bronisława Skrzep-Poloczek ◽

Aleksander J. Owczarek ◽

Natalia Matysiak ◽

...

Keyword(s):

Body Weight ◽

Glucose Tolerance ◽

High Fat Diet ◽

Control Diet ◽

Sprague Dawley ◽

High Fat ◽

Sprague Dawley Rats ◽

And Control

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Betaine improved adipose tissue function in mice fed a high-fat diet: a mechanism for hepatoprotective effect of betaine in nonalcoholic fatty liver disease

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00249.2009 ◽

2010 ◽

Vol 298 (5) ◽

pp. G634-G642 ◽

Cited By ~ 85

Author(s):

Zhigang Wang ◽

Tong Yao ◽

Maria Pini ◽

Zhanxiang Zhou ◽

Giamila Fantuzzi ◽

...

Keyword(s):

Insulin Resistance ◽

Adipose Tissue ◽

Liver Disease ◽

Fatty Liver ◽

High Fat Diet ◽

Fatty Liver Disease ◽

Control Diet ◽

High Fat ◽

Nonalcoholic Fatty Liver ◽

Betaine Supplementation

Adipose tissue dysfunction, featured by insulin resistance and/or dysregulated adipokine production, plays a central role not only in disease initiation but also in the progression to nonalcoholic steatohepatitis and cirrhosis. Promising beneficial effects of betaine supplementation on nonalcoholic fatty liver disease (NAFLD) have been reported in both clinical investigations and experimental studies; however, data related to betaine therapy in NAFLD are still limited. In this study, we examined the effects of betaine supplementation on hepatic fat accumulation and injury in mice fed a high-fat diet and evaluated mechanisms underlying its hepatoprotective effects. Male C57BL/6 mice weighing 25 ± 0.5 (SE) g were divided into four groups (8 mice/group) and started on one of four treatments: control diet, control diet supplemented with betaine, high-fat diet, and high-fat diet supplemented with betaine. Betaine was supplemented in the drinking water at a concentration of 1% (wt/vol) (anhydrous). Our results showed that long-term high-fat feeding caused NAFLD in mice, which was manifested by excessive neutral fat accumulation in the liver and elevated plasma alanine aminotransferase levels. Betaine supplementation alleviated hepatic pathological changes, which were concomitant with attenuated insulin resistance as shown by improved homeostasis model assessment of basal insulin resistance values and glucose tolerance test, and corrected abnormal adipokine (adiponectin, resistin, and leptin) productions. Specifically, betaine supplementation enhanced insulin sensitivity in adipose tissue as shown by improved extracellular signal-regulated kinases 1/2 and protein kinase B activations. In adipocytes freshly isolated from mice fed a high-fat diet, pretreatment of betaine enhanced the insulin signaling pathway and improved adipokine productions. Further investigation using whole liver tissues revealed that betaine supplementation alleviated the high-fat diet-induced endoplasmic reticulum stress response in adipose tissue as shown by attenuated glucose-regulated protein 78/C/EBP homologous protein (CHOP) protein abundance and c-Jun NH2-terminal kinase activation. Our findings suggest that betaine might serve as a safe and efficacious therapeutic tool for NAFLD by improving adipose tissue function.

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Effects of a High-Fat Diet Exposure in Utero on the Metabolic Syndrome-Like Phenomenon in Mouse Offspring through Epigenetic Changes in Adipocytokine Gene Expression

Endocrinology ◽

10.1210/en.2011-2161 ◽

2012 ◽

Vol 153 (6) ◽

pp. 2823-2830 ◽

Cited By ~ 124

Author(s):

Hisashi Masuyama ◽

Yuji Hiramatsu

Keyword(s):

Gene Expression ◽

Metabolic Syndrome ◽

High Fat Diet ◽

Control Diet ◽

Caloric Intake ◽

In Utero ◽

Shared Environment ◽

Epigenetic Changes ◽

High Fat ◽

The Metabolic Syndrome

The links between obesity in parents and their offspring and the role of genes and a shared environment are not completely understood. Adipocytokines such as leptin and adiponectin play important roles in glucose and lipid metabolism. Therefore, we examined whether the offspring from dams exposed to a high-fat diet during pregnancy (OH mice) exhibited hypertension, insulin resistance, and hyperlipidemia along with epigenetic changes in the expression of adipocytokine genes. OH mice were significantly heavier than the offspring of dams exposed to a control diet during pregnancy (OC mice) from 14 wk of age after an increased caloric intake from 8 wk. OH mice exhibited higher blood pressure and worse glucose tolerance than the OC mice at 24 wk. Total triglyceride and leptin levels were significantly higher and the adiponectin level was significantly lower in OH compared with OC mice at 12 wk of age. This was associated with changes in leptin and adiponectin expression in white adipose tissue. There were lower acetylation and higher methylation levels of histone H3 at lysine 9 of the promoter of adiponectin in adipose tissues of OH mice at 2 wk of age as well as at 12 and 24 wk of age compared with OC mice. In contrast, methylation of histone 4 at lysine 20 in the leptin promoter was significantly higher in OH compared with OC mice. Thus, exposure to a high-fat diet in utero might cause a metabolic syndrome-like phenomenon through epigenetic modifications of adipocytokine, adiponectin, and leptin gene expression.

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