Increasing the fat-to-carbohydrate ratio in a high-fat diet prevents the development of obesity but not a prediabetic state in rats

2007 ◽  
Vol 113 (10) ◽  
pp. 417-425 ◽  
Author(s):  
Natalia Sinitskaya ◽  
Sylviane Gourmelen ◽  
Carole Schuster-Klein ◽  
Béatrice Guardiola-Lemaitre ◽  
Paul Pévet ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Control Diet ◽  
High Fat ◽  
Carbohydrate Diet ◽  
Prediabetic State ◽  
Plasma Leptin ◽  
Very High

Metabolic disorders induced by high-fat feeding in rodents evoke some, if not all, of the features of human metabolic syndrome. The occurrence and severity of metabolic disorders, however, varies according to rodent species, and even strain, as well as the diet. Therefore, in the present study, we investigated the long-term obesogenic and diabetogenic effects of three high-fat diets differing by their fat/carbohydrate ratios. Sprague–Dawley rats were fed a control high-carbohydrate and low-fat diet [HCD; 3:16:6 ratio of fat/carbohydrate/protein; 15.48 kJ/g (3.7 kcal/g)], a high-fat and medium-carbohydrate diet [HFD1; 53:30:17 ratio of fat/carbohydrate/protein; 19.66 kJ/g (4.7 kcal/g)], a very-high-fat and low-carbohydrate diet [HFD2; 67:9:24 ratio of fat/carbohydrate/protein; 21.76 kJ/g (5.2 kcal/g)] or a very-high-fat and carbohydrate-free diet [HFD3; 75:0:25 ratio of fat/carbohydrate/protein; 24.69 kJ/g (5.9 kcal/g)] for 10 weeks. Compared with the control diet (HCD), rats fed with high-fat combined with more (HFD1) or less (HFD2) carbohydrate exhibited higher BMI (body mass index; +13 and +10% respectively; P<0.05) and abdominal fat (+70% in both HFD1 and HFD2; P<0.05), higher plasma leptin (+130 and +135% respectively; P<0.05), lower plasma adiponectin levels (−23 and −30% respectively; P<0.05) and impaired glucose tolerance. Only the HFD1 group had insulin resistance. By contrast, a very-high-fat diet devoid of carbohydrate (HFD3) led to impaired glucose tolerance, insulin resistance and hypoadiponectinaemia (−50%; P<0.05), whereas BMI, adiposity and plasma leptin did not differ from respective values in animals fed the control diet. We conclude that increasing the fat-to-carbohydrate ratio to the uppermost (i.e. carbohydrate-free) in a high-fat diet prevents the development of obesity, but not the prediabetic state (i.e. altered glucose tolerance and insulin sensitivity).

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

2005 ◽  
Vol 17 (9) ◽  
pp. 105 ◽  
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.

A modified high-fat diet induces insulin resistance in rat skeletal muscle but not adipocytes

1998 ◽  
Vol 275 (4) ◽  
pp. E679-E686 ◽  
Author(s):  
Jason J. Wilkes ◽  
Arend Bonen ◽  
Rhonda C. Bell
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Glucose Tolerance ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Uptake ◽  
High Fat Diet ◽  
Control Diet ◽  
Mixed Diet ◽  
High Fat

We hypothesized that variation in dietary fatty acid composition in rats fed a high-fat diet had tissue-specific effects on glucose uptake sufficient to maintain normal glucose tolerance. Rats were fed one of three diets for 3 wk. The isocaloric high-fat-mixed oil (HF-mixed) diet and the high-fat-safflower oil (HF-saff) diet both provided 60% kcal fat, but fat composition differed [HF-mixed = saturated, polyunsaturated (n-3 and n-6), and monounsaturated fatty acids; HF-saff = polyunsaturated fatty acids (mainly n-6)]. The control diet was high carbohydrate (HCHO, 10% kcal fat). Insulin-stimulated 3- O-methylglucose uptake into perfused hindlimb muscles was reduced in rats fed HF-saff and HF-mixed diets compared with those fed HCHO diet ( P< 0.02). Basal uptake increased in HF-saff- and HF-mixed-fed rats vs. HCHO-fed rats ( P < 0.04). In adipocytes, HF-saff feeding decreased 2-deoxyglucose uptake vs. HF-mixed feeding and HCHO feeding ( P< 0.05), but 2-deoxyglucose uptake in HF-mixed-fed rats did not differ from that in HCHO-fed rats ( P> 0.05). Glucose tolerance was significantly reduced in HF-saff-fed rats but was unaffected by the HF-mixed diet. Therefore, in skeletal muscle of rats, 1) feeding a diet high in fat induces a reduction in insulin-stimulated glucose uptake but 2) provides an increase in basal glucose uptake. In contrast, 3) in adipocytes, insulin-stimulated glucose transport is reduced only when the high-fat diet is high in n-6 polyunsaturated fatty acids but not when fat comes from these mixed sources. Glucose intolerance becomes evident when insulin resistance is seen in multiple tissues.

scholarly journals Methionine restriction plus overload improves skeletal muscle and metabolic health in old mice on a high fat diet

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Anandini Swaminathan ◽  
Andrej Fokin ◽  
Tomas Venckūnas ◽  
Hans Degens
Keyword(s):  
Skeletal Muscle ◽  
Glucose Tolerance ◽  
Muscle Mass ◽  
Body Mass ◽  
High Fat Diet ◽  
Control Diet ◽  
Metabolic Health ◽  
High Fat ◽  
Methionine Restriction ◽  
Old Mice

AbstractMethionine restriction (MR) has been shown to reduce the age-induced inflammation. We examined the effect of MR (0.17% methionine, 10% kCal fat) and MR + high fat diet (HFD) (0.17% methionine, 45% kCal fat) on body mass, food intake, glucose tolerance, resting energy expenditure, hind limb muscle mass, denervation-induced atrophy and overload-induced hypertrophy in young and old mice. In old mice, MR and MR + HFD induced a decrease in body mass. Muscle mass per body mass was lower in old compared to young mice. MR restored some of the HFD-induced reduction in muscle oxidative capacity. The denervation-induced atrophy of the m. gastrocnemius was larger in animals on MR than on a control diet, irrespective of age. Old mice on MR had larger hypertrophy of m. plantaris. Irrespective of age, MR and MR + HFD had better glucose tolerance compared to the other groups. Young and old mice on MR + HFD had a higher resting VO2 per body mass than HFD group. Mice on MR and MR + HFD had a resting respiratory quotient closer to 0.70, irrespective of age, indicating an increased utilization of lipids. In conclusion, MR in combination with resistance training may improve skeletal muscle and metabolic health in old age even in the face of obesity.

Insulin Resistance Precedes Liver Adaptations After One Week of Exposure to a Very High-fat Diet

2011 ◽  
Vol 43 (Suppl 1) ◽  
pp. 482
Author(s):  
Melissa A. Linden ◽  
Yair Pincu ◽  
Stephen A. Martin ◽  
Jeffrey A. Woods ◽  
Tracy Baynard
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
High Fat ◽  
Very High

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 ◽  
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.

Resveratrol ameliorates metabolic disorders and insulin resistance in high-fat diet-fed mice

Life Sciences ◽  
2020 ◽  
Vol 242 ◽  
pp. 117212 ◽  
Author(s):  
Longlong Gong ◽  
Shuang Guo ◽  
Zhengzhi Zou
Keyword(s):  
Insulin Resistance ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
High Fat

scholarly journals Disrupting phosphatase SHP2 in macrophages protects mice from high-fat diet-induced hepatic steatosis and insulin resistance by elevating IL-18 levels

2020 ◽  
Vol 295 (31) ◽  
pp. 10842-10856 ◽  
Author(s):  
Wen Liu ◽  
Ye Yin ◽  
Meijing Wang ◽  
Ting Fan ◽  
Yuyu Zhu ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Metabolic Disorders ◽  
Metabolic Diseases ◽  
Low Grade ◽  
High Fat ◽  
Caspase 1

Chronic low-grade inflammation plays an important role in the pathogenesis of type 2 diabetes. Src homology 2 domain-containing tyrosine phosphatase-2 (SHP2) has been reported to play diverse roles in different tissues during the development of metabolic disorders. We previously reported that SHP2 inhibition in macrophages results in increased cytokine production. Here, we investigated the association between SHP2 inhibition in macrophages and the development of metabolic diseases. Unexpectedly, we found that mice with a conditional SHP2 knockout in macrophages (cSHP2-KO) have ameliorated metabolic disorders. cSHP2-KO mice fed a high-fat diet (HFD) gained less body weight and exhibited decreased hepatic steatosis, as well as improved glucose intolerance and insulin sensitivity, compared with HFD-fed WT littermates. Further experiments revealed that SHP2 deficiency leads to hyperactivation of caspase-1 and subsequent elevation of interleukin 18 (IL-18) levels, both in vivo and in vitro. Of note, IL-18 neutralization and caspase-1 knockout reversed the amelioration of hepatic steatosis and insulin resistance observed in the cSHP2-KO mice. Administration of two specific SHP2 inhibitors, SHP099 and Phps1, improved HFD-induced hepatic steatosis and insulin resistance. Our findings provide detailed insights into the role of macrophagic SHP2 in metabolic disorders. We conclude that pharmacological inhibition of SHP2 may represent a therapeutic strategy for the management of type 2 diabetes.

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

2019 ◽  
Vol 317 (6) ◽  
pp. C1172-C1182 ◽  
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.

scholarly journals Hypoglycemic effects and mechanisms of electroacupuncture on insulin resistance

2014 ◽  
Vol 307 (3) ◽  
pp. R332-R339 ◽  
Author(s):  
Jieyun Yin ◽  
Jian Kuang ◽  
Manisha Chandalia ◽  
Demidmaa Tuvdendorj ◽  
Batbayar Tumurbaatar ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acid ◽  
Blood Glucose ◽  
Insulin Sensitivity ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
High Fat Diet ◽  
Postprandial Glucose ◽  
Tolerance Test ◽  
High Fat

The aim of this study was to investigate effects and mechanisms of electroacupuncture (EA) on blood glucose and insulin sensitivity in mice fed a high-fat diet. Both wild-type (WT) and adipose ectonucleotide pyrophosphate phosphodiesterase (ENPP1) transgenic (TG) mice were fed a high-fat diet for 12 wk; for each mouse, an intraperitoneal glucose tolerance test (IPGTT) and insulin tolerance test (ITT) were performed with or without EA at abdomen or auricular areas. A high-fat diet-induced insulin resistance in both WT and TG mice. In the WT mice, EA at 3 Hz and 15 Hz, but not at 1 Hz or 100 Hz, via CV4+CV12 significantly reduced postprandial glucose levels; EA at 3 Hz was most potent. The glucose level was reduced by 61.7% at 60 min and 74.5% at 120 min with EA at 3 Hz (all P < 0.001 vs. control). Similar hypoglycemic effect was noted in the TG mice. On the contrary, EA at auricular points increased postprandial glucose level ( P < 0.03). 4). EA at 3 Hz via CV4+CV12 significantly enhanced the decrease of blood glucose after insulin injection, suggesting improvement of insulin sensitivity. Plasma free fatty acid was significantly suppressed by 42.5% at 15 min and 50.8% at 30 min with EA ( P < 0.01) in both WT and TG mice. EA improves glucose tolerance in both WT and TG mice fed a high-fat diet, and the effect is associated with stimulation parameters and acupoints and is probably attributed to the reduction of free fatty acid.

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