Resistance to high-fat diet in the female progeny of obese mice fed a control diet during the periconceptual, gestation, and lactation periods

With the worldwide epidemic of metabolic syndrome (MetS), the proportion of women that are overweight/obese and overfed during pregnancy has increased. The resulting abnormal uterine environment may have deleterious effects on fetal metabolic programming and lead to MetS in adulthood. A balanced/restricted diet and/or physical exercise often improve metabolic abnormalities in individuals with obesity and type 2 diabetes mellitus (T2D). We investigated whether reducing fat intake during the periconceptual/gestation/lactation period in mothers with high-fat diet (HFD)-induced obesity could be used to modify fetal/neonatal MetS programming positively, thereby preventing MetS. First generation (F1) C57BL/6J female mice with HFD-induced obesity and T2D were crossed with F1 males on control diet (CD). These F1 females were switched to a CD during the periconceptual/gestation/lactation period. At weaning, both male and female second generation (F2) mice were fed a HFD. Weight, caloric intake, lipid parameters, glucose, and insulin sensitivity were assessed. Sensitivity/resistance to the HFD differed significantly between generations and sexes. A similar proportion of the F1 and F2 males (80%) developed hyperphagia, obesity, and T2D. In contrast, a significantly higher proportion of the F2 females (43%) than of the previous F1 generation (17%) were resistant ( P < 0.01). Despite having free access to the HFD, these female mice were no longer hyperphagic and remained lean, with normal insulin sensitivity and glycemia but mild hypercholesterolemia and glucose intolerance, thus displaying a “satiety phenotype.” This suggests that an appropriate dietary fatty acid profile and intake during the periconceptual/gestation/lactation period helps the female offspring to cope with deleterious intrauterine conditions.

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Abstract 58: Angiotensin-(1-7) Mas Receptors In The Arcuate Nucleus Of The Hypothalamus Protect Against High Fat Diet-induced Insulin Resistance In Female Mice

Hypertension ◽

10.1161/hyp.78.suppl_1.58 ◽

2021 ◽

Vol 78 (Suppl_1) ◽

Author(s):

Darren Mehay ◽

Sarah Bingaman ◽

Yuval Silberman ◽

Amy Arnold

Keyword(s):

Body Composition ◽

Insulin Sensitivity ◽

Energy Balance ◽

Glucose Tolerance ◽

High Fat Diet ◽

Metabolic Regulation ◽

Arcuate Nucleus ◽

Control Diet ◽

High Fat ◽

Metabolic Outcomes

Angiotensin (Ang)-(1-7) is a protective hormone of the renin-angiotensin system that improves insulin sensitivity, glucose tolerance, and energy balance in obese rodents. Our recent findings suggest that Ang-(1-7) activates mas receptors (MasR) in the arcuate nucleus of the hypothalamus (ARC), a brain region critical to control of energy balance and glucose homeostasis, to induce these positive metabolic effects. The distribution of MasR in the ARC and their role in metabolic regulation, however, is unknown. We hypothesized: (1) MasR are expressed in the ARC; and (2) deletion of ARC MasR leads to worsened metabolic outcomes following high fat diet (HFD). To test this, male and female C57Bl/6J mice were fed a 60% HFD or matched control diet ad libitum for 12 weeks. RNAscope in situ hybridization was performed on coronal ARC sections in rostral-middle-caudal regions to determine percentage of MasR positive neurons (n=5/group). In a second experiment, we assessed body composition and insulin and glucose tolerance in transgenic mice with deletion of MasR in ARC neurons (MasR-flox with AAV5-hsyn-GFP-Cre). RNAscope revealed a wide distribution on MasR-positive cells throughout the rostral to caudal extent of the ARC. The average percentage of MasR positive neurons was increased in females versus males, with HFD tending to increase MasR expression in both sexes (control diet male: 11±2; control diet female: 17±3; HFD male: 15±5; HFD female: 24±2; p sex : 0.030; p diet : 0.066; p int : 0.615; two-way ANOVA). Deletion of MasR in ARC neurons worsened insulin sensitivity in HFD but not control diet females (area under the curve for change in glucose from baseline: -1989±1359 HFD control virus vs. 2530±1762 HFD Cre virus; p=0.016), while fasting glucose, glucose tolerance, and body composition did not change. There was no effect of ARC MasR deletion on metabolic outcomes in control diet or HFD male mice. These findings suggest females have more MasR positive neurons in the ARC compared to males, which may be a sex-specific protective mechanism for glucose homeostasis. While further studies are needed to explore the role of ARC MasR in metabolic regulation, these findings support targeting Ang-(1-7) as an innovative strategy in obesity.

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

International Journal of Obesity ◽

10.1038/ijo.2017.179 ◽

2017 ◽

Vol 41 (12) ◽

pp. 1805-1814 ◽

Cited By ~ 6

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

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

Physiological Genomics ◽

10.1152/physiolgenomics.00135.2017 ◽

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.

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Macadamia Oil Supplementation Attenuates Inflammation and Adipocyte Hypertrophy in Obese Mice

Mediators of Inflammation ◽

10.1155/2014/870634 ◽

2014 ◽

Vol 2014 ◽

pp. 1-9 ◽

Cited By ~ 11

Author(s):

Edson A. Lima ◽

Loreana S. Silveira ◽

Laureane N. Masi ◽

Amanda R. Crisma ◽

Mariana R. Davanso ◽

...

Keyword(s):

Adipose Tissue ◽

Insulin Sensitivity ◽

Lipid Profile ◽

High Fat Diet ◽

Control Diet ◽

Saturated Fatty Acids ◽

Peritoneal Macrophages ◽

High Fat ◽

Obesity In Mice ◽

Adipocyte Hypertrophy

Excess of saturated fatty acids in the diet has been associated with obesity, leading to systemic disruption of insulin signaling, glucose intolerance, and inflammation. Macadamia oil administration has been shown to improve lipid profile in humans. We evaluated the effect of macadamia oil supplementation on insulin sensitivity, inflammation, lipid profile, and adipocyte size in high-fat diet (HF) induced obesity in mice. C57BL/6 male mice (8 weeks) were divided into four groups: (a) control diet (CD), (b) HF, (c) CD supplemented with macadamia oil by gavage at 2 g/Kg of body weight, three times per week, for 12 weeks (CD + MO), and (d) HF diet supplemented with macadamia oil (HF + MO). CD and HF mice were supplemented with water. HF mice showed hypercholesterolemia and decreased insulin sensitivity as also previously shown. HF induced inflammation in adipose tissue and peritoneal macrophages, as well as adipocyte hypertrophy. Macadamia oil supplementation attenuated hypertrophy of adipocytes and inflammation in the adipose tissue and macrophages.

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

Arteriosclerosis Thrombosis and Vascular Biology ◽

10.1161/atvbaha.121.316896 ◽

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.

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Phytochemicals in fenugreek seed prevent high fat diet induced metabolic inflammation and NAFLD via the mediation of Akkermansia muciniphila

Proceedings of The Nutrition Society ◽

10.1017/s0029665120004334 ◽

2020 ◽

Vol 79 (OCE2) ◽

Author(s):

Qiaozhu Su

Keyword(s):

Body Weight ◽

Insulin Sensitivity ◽

Bioactive Compounds ◽

High Fat Diet ◽

De Novo ◽

Caloric Intake ◽

High Fat ◽

Feeding Trial ◽

Metabolic Inflammation ◽

Fenugreek Seed

AbstractIntroductionFenugreek (Trigonella foenum-graecum) is an annual legume that has been used as a spice throughout the world to enhance the sensory quality of foods. A number of health-beneficial bioactive compounds (i.e. trigonelline and diosgenin) have been identified in the seed of fenugreek. These compounds exert multiple health beneficial effects, including anti-obesity and anti-type 2 diabetes. The objective of our study is to determine the underlying mechanism of whole grain of fenugreek seed and purified bioactive compounds, trigonelline and diosgenin, in ameliorating high fat diet (HFD) induced metabolic inflammation and non-alcoholic fatty liver disease (NAFLD).Materials and MethodsTwo groups of C57B6 mice were fed a HFD containing either a vehicle control or 2% of fenugreek seed for 7 weeks. Caloric intake and body weight were monitored weekly during the feeding trial. Glucose tolerance test was conducted to determine the insulin sensitivity. Q-RT-PCR, immunoblotting analysis and histological analysis were used to determine the expression of genes involved in metabolic inflammation and lipid metabolism.Results and DiscussionWhile caloric intake and body weight were comparable between control and fenugreek treated groups during the feeding trial, fenugreek seed containing diet significantly reduced circulation level of inflammatory cytokine TNFa. In the liver, fenugreek suppressed the gene expression of inflammatory cytokines, such as IL-1b and IL-6, and ameliorated hepatic ER stress. The improvement of metabolic inflammation was associated with less activation of genes involved in hepatic de novo lipid synthesis (i.e. FASN and ACC) and enhanced fatty b-oxidation which resulted in significant amelioration of HFD-induced hepatic steatosis, hyperlipidemia and insulin resistance. Analysis the populations of gut microbiota further revealed that the population of Akkermansia muciniphila, a gut bacterial strain that is involved in body weight regulation and insulin sensitivity, was significantly increased by fenugreek seed containing diet. In vitro, treating McA-RH7777, a rat hepatoma cell line, with purified phytochemicals of fenugreek seeds, trigonelline and diosgenin, inhibited hepatic de novo lipogenesis, attenuated ER stress induced by a saturated fatty acid, palmitic acid. These actions improved insulin sensitivity in McA-RH7777 cells by enhancing the functional activity of insulin signaling molecules, such as insulin receptor and AKT.ConclusionOur study unveils a novel mechanism of the bioactive compounds, trigonelline and diosgenin, in fenugreek seed that ameliorate metabolic inflammation and hepatic steatosis via the mediation of gut bacteria. This finding may lend support for developing phytochemicals in fenugreek seed as prebiotic supplement for the prevention and treatment of hyperlipidemia and insulin resistance.

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Grape Juice Consumption with or without High Fat Diet during Pregnancy Reduced the Weight Gain and Improved Lipid Profile and Oxidative Stress Levels in Liver and Serum from Wistar Rats

Beverages ◽

10.3390/beverages4040078 ◽

2018 ◽

Vol 4 (4) ◽

pp. 78 ◽

Cited By ~ 2

Author(s):

Luciana Gonçalves ◽

Gabrielli Bortolato ◽

Ruben Dario Braccini Neto ◽

Marina Rocha Frusciante ◽

Claudia Funchal ◽

...

Keyword(s):

Oxidative Stress ◽

Weight Gain ◽

High Fat Diet ◽

Wistar Rats ◽

Control Diet ◽

Grape Juice ◽

Free Access ◽

Tbars Level ◽

High Fat ◽

And Oxidative Stress

The aim of this study was to evaluate the effects of high fat diet with or without grape juice during the pregnancy on gestational weight gain, biochemical parameters, and oxidative stress in plasma and liver from Wistar rats. Forty-nine rats were divided into four groups: control diet group (CD), high fat diet (HFD), grape juice and control diet (PGJCD), and grape juice and high fat diet (PGJHFD). During the treatment the weight gain of the rats was tracked. They had free access to their respective diets during 42 days of treatment. After offspring weaning, the mother rats were euthanized and blood and liver were collected. The high fat diet increased the total cholesterol and triglycerides serum levels as well as carbonyl levels in the liver, however this diet reduced the high-density lipoprotein (HDL) and urea levels in serum. Grape juice consumption reduced gestational body weight gain. In liver, the juice consumption increased sulfhydryl levels and reduced the superoxide dismutase (SOD) activity and TBARS level, in serum the consumption reduced aspartate aminotransferase (AST) and TBARS. We can conclude that the consumption of a diet rich in fat can promotes harmful effects on health during pregnancy, however the consumption of grape juice seems to be an important alternative to prevent oxidative damages and to promote the improvement of health.

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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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Composition of a maternal high fat diet rich in satured fats and omega 3 in gestation and lactation for studies with rodents

Revista de Nutrição ◽

10.1590/1678-9865201932e180292 ◽

2019 ◽

Vol 32 ◽

Author(s):

Laura Mata de Lima SILVA ◽

Aline Maria Nunes de Lira Gomes BLOISE ◽

Danilo Augusto Ferreira FONTES ◽

Katarynna Santos de ARAÚJO ◽

Mariana Oliveira BARBOSA ◽

...

Keyword(s):

Fatty Acids ◽

Body Mass ◽

High Fat Diet ◽

Control Diet ◽

Saturated Fatty Acids ◽

Experimental Studies ◽

Abdominal Circumference ◽

Lactation Period ◽

Omega 3 ◽

High Fat

ABSTRACT Objective To prepare a high fat diet rich in satured fatty acids and supplemented with omega 3 for experimental studies in rodents. Methods Purified industrial ingredients and flaxseed oil as a source of omega 3 at a concentration of 3.5% (v/w) were used in the elaboration of the diets. Centesimal and nutritional compositions, fatty acids profile and dietary intake were evaluated. Serum levels of total protein, albumin, cholesterol and glucose in pregnant rats were verified. The offspring were assessed with regard to body mass and waist circumference. Statistical analysis was performed using the Kolmogorov-Smirnov, Anova One-Way test and Bonferroni post-test. Results High fat and high fat with omega 3 diets presented, respectively, 37% and 36% saturated fat, and the lipid amount was 80% higher than the American Institute of Nutrition 93G control diet. The omega 3 content was 50% higher in the high fat with omega 3 diet. There was no difference in consumption of diet types in weight (grams). The dams that received the High fat diet developed hypercholesterolemia and their High fat offspring exhibited higher body mass on the 1st day of life and increased abdominal circumference on the 30th day of life compared to the control and the high fat with omega 3 offspring. Conclusion The formulated diets with a higher amount of saturated fatty acids meet the nutritional requirements of the gestation and lactation period. The high fat diet with omega 3 was able to attenuate the changes observed in dams and their offspring.

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