Sexual dimorphism in insulin resistance in a metabolic syndrome rat model

Objective: We assessed the sex-specific differences in the molecular mechanisms of insulin resistance in muscle and adipose tissue, in a MS rat model induced by a high sucrose diet. Methods: Male, female, and ovariectomized female Wistar rats were randomly distributed in control and high-sucrose diet (HSD) groups, supplemented for 24 weeks with 20% sucrose in the drinking water. At the end, we assessed parameters related to MS, analyzing the effects of the HSD on critical nodes of the insulin signaling pathway in muscle and adipose tissue. Results: At the end of the treatment, HSD groups of both sexes developed obesity, with a 15, 33 and 23% of body weight gain in male, female, and OVX groups respectively, compared with controls; mainly related to hypertrophy of peripancreatic and gonadal adipose tissue. They also developed hypertriglyceridemia, and liver steatosis, with the last being worse in the HSD females. Compared to the control groups, HSD rats had higher IL1B and TNFA levels and insulin resistance. HSD females were more intolerant to glucose than HSD males. Our observations suggest that insulin resistance mechanisms include an increase in phosphorylated AKT(S473) form in HSD male and female groups and a decrease in phosphorylated P70S6K1(T389) in the HSD male groups from peripancreatic adipose tissue. While in gonadal adipose tissue the phosphorylated form of AKT decreased in HSD females, but not in HSD males. Finally, HSD groups showed a reduction in p-AKT levels in gastrocnemius muscle. Conclusion: A high-sucrose diet induces MS and insulin resistance with sex-associated differences and in a tissue-specific manner.

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Reduced insulin suppression of glucose appearance is related to susceptibility to dietary obesity in rats

AJP Regulatory Integrative and Comparative Physiology ◽

10.1152/ajpregu.1997.272.4.r1264 ◽

1997 ◽

Vol 272 (4) ◽

pp. R1264-R1270 ◽

Cited By ~ 3

Author(s):

M. J. Pagliassotti ◽

T. J. Horton ◽

E. C. Gayles ◽

T. A. Koppenhafer ◽

T. D. Rosenzweig ◽

...

Keyword(s):

Insulin Resistance ◽

Body Weight ◽

Weight Gain ◽

Energy Intake ◽

Body Weight Gain ◽

Hepatic Insulin Resistance ◽

Glucose Kinetics ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

To examine the relationship between insulin action and body weight regulation in male rats, the following studies were performed. In study 1, rats (n = 31) were fed a low-fat diet (LFD) for 4 wk, and then glucose kinetics were estimated under basal and hyperinsulinemic conditions using the glucose clamp. After clamps, these same rats were placed on a high-fat diet (HFD) for 5 wk. In study 2, rats (n = 30) were fed an LFD for 3 wk and then a high-sucrose diet for 1 wk to produce selective hepatic insulin resistance. Clamps were then performed, and after clamps, these same rats were placed on an HFD for 5 wk. In study 3, rats (n = 30) were fed an LFD for 1 wk and then a high-sucrose diet for 3 wk to produce widespread insulin resistance. Clamps were then performed, and after clamps, these same rats were placed on an HFD for 5 wk. The rate of glucose appearance (R(a)) during the hyperinsulinemic clamps was the only pre-HFD variable that correlated (r = 0.49, P < 0.01 in study 1; r = 0.51, P < 0.001 in study 2) with weight gain on the HFD. Clamp R(a) also correlated with energy intake on the HFD in study 1 (r = 0.64, P < 0.001) and study 2 (r = 0.59, P < 0.001). Clamp R(a) and energy intake on the HFD accounted for similar portions of the variance in body weight gain on the HFD. Weight gain and fat-pad mass were increased (P < 0.05) in study 2 compared with study 1. In study 3, pre-HFD glucose kinetics were not correlated with energy intake or weight gain on the HFD. Widespread insulin resistance did not significantly reduce the rate of weight gain on the HFD. Thus insulin action on R(a) can influence body weight gain on an HFD. The effects of R(a) on body weight gain appear to be mediated via effects on energy intake. Selective hepatic insulin resistance can increase body weight gain on an HFD, but widespread insulin resistance does not significantly reduce HFD-induced weight gain.

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Impact of Saskatoon Berry Powder on Insulin Resistance and Intestinal Microbiome in High-Fat, High-Sucrose Diet-Induced Obese and Insulin-Resistant Mice

Canadian Journal of Diabetes ◽

10.1016/j.jcjd.2018.08.087 ◽

2018 ◽

Vol 42 (5) ◽

pp. S31

Author(s):

Ruozhi Zhao ◽

Ehsan Khafipour ◽

Shadi Sepehri ◽

Fei Huang ◽

Trust Beta ◽

...

Keyword(s):

Insulin Resistance ◽

Intestinal Microbiome ◽

High Fat ◽

Insulin Resistant ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

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Adiponectin induced AMP-activated protein kinase impairment mediates insulin resistance in Bama mini-pig fed high-fat and high-sucrose diet

Asian-Australasian Journal of Animal Sciences ◽

10.5713/ajas.17.0006 ◽

2017 ◽

Vol 30 (8) ◽

pp. 1190-1197 ◽

Cited By ~ 5

Author(s):

Miaomiao Niu ◽

Lei Xiang ◽

Yaqian Liu ◽

Yuqiong Zhao ◽

Jifang Yuan ◽

...

Keyword(s):

Insulin Resistance ◽

Protein Kinase ◽

High Fat ◽

Sucrose Diet ◽

High Sucrose Diet ◽

Amp Activated Protein Kinase ◽

High Sucrose

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Characterization of free fatty acid receptors expression in an obesity rat model with high sucrose diet

Journal of Receptors and Signal Transduction ◽

10.1080/10799893.2018.1426609 ◽

2018 ◽

Vol 38 (1) ◽

pp. 76-82

Author(s):

Fabián Meza-Cuenca ◽

J. M. L. Medina-Contreras ◽

Patrick Mailloux-Salinas ◽

Luis A. Bautista-Hernández ◽

Beatríz Buentello-Volante ◽

...

Keyword(s):

Fatty Acid ◽

Free Fatty Acid ◽

Rat Model ◽

Sucrose Diet ◽

High Sucrose Diet ◽

Free Fatty Acid Receptors ◽

High Sucrose

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High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model

Bone and Joint Research ◽

10.1302/2046-3758.74.bjr-2017-0201.r2 ◽

2018 ◽

Vol 7 (4) ◽

pp. 274-281 ◽

Cited By ~ 18

Author(s):

K. H. Collins ◽

D. A. Hart ◽

R. A. Seerattan ◽

R. A. Reimer ◽

W. Herzog

Keyword(s):

Rat Model ◽

Joint Damage ◽

Knee Joints ◽

High Fat ◽

Mankin Score ◽

Diet Induced Obesity ◽

Sucrose Diet ◽

High Sucrose Diet ◽

Predictive Relationships ◽

High Sucrose

Objectives Metabolic syndrome and low-grade systemic inflammation are associated with knee osteoarthritis (OA), but the relationships between these factors and OA in other synovial joints are unclear. The aim of this study was to determine if a high-fat/high-sucrose (HFS) diet results in OA-like joint damage in the shoulders, knees, and hips of rats after induction of obesity, and to identify potential joint-specific risks for OA-like changes. Methods A total of 16 male Sprague-Dawley rats were allocated to either the diet-induced obesity group (DIO, 40% fat, 45% sucrose, n = 9) or a chow control diet (n = 7) for 12 weeks. At sacrifice, histological assessments of the shoulder, hip, and knee joints were performed. Serum inflammatory mediators and body composition were also evaluated. The total Mankin score for each animal was assessed by adding together the individual Modified Mankin scores across all three joints. Linear regression modelling was conducted to evaluate predictive relationships between serum mediators and total joint damage. Results The HFS diet, in the absence of trauma, resulted in increased joint damage in the shoulder and knee joints of rats. Hip joint damage, however, was not significantly affected by DIO, consistent with findings in human studies. The total Mankin score was increased in DIO animals compared with the chow group, and was associated with percentage of body fat. Positive significant predictive relationships for total Mankin score were found between body fat and two serum mediators (interleukin 1 alpha (IL-1α) and vascular endothelial growth factor (VEGF)). Conclusion Systemic inflammatory alterations from DIO in this model system may result in a higher risk for development of knee, shoulder, and multi-joint damage with a HFS diet. Cite this article: K. H. Collins, D. A. Hart, R. A. Seerattan, R. A. Reimer, W. Herzog. High-fat/high-sucrose diet-induced obesity results in joint-specific development of osteoarthritis-like degeneration in a rat model. Bone Joint Res 2018;7:274–281. DOI: 10.1302/2046-3758.74.BJR-2017-0201.R2

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Nutritional and metabolic regulation of the metabolite dimethylguanidino valeric acid: an early marker of cardiometabolic disease

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00207.2020 ◽

2020 ◽

Vol 319 (3) ◽

pp. E509-E518

Author(s):

Jibran A. Wali ◽

Yen Chin Koay ◽

Jason Chami ◽

Courtney Wood ◽

Leo Corcilius ◽

...

Keyword(s):

Insulin Resistance ◽

Metabolic Regulation ◽

Fruits And Vegetables ◽

Valeric Acid ◽

High Fiber ◽

Sucrose Diet ◽

Comprehensive Picture ◽

High Sucrose Diet ◽

Sugary Beverages ◽

High Sucrose

Dimethylguanidino valeric acid (DMGV) is a marker of fatty liver disease, incident coronary artery disease, cardiovascular mortality, and incident diabetes. Recently, it was reported that circulating DMGV levels correlated positively with consumption of sugary beverages and negatively with intake of fruits and vegetables in three Swedish community-based cohorts. Here, we validate these results in the Framingham Heart Study Third Generation Cohort. Furthermore, in mice, diets rich in sucrose or fat significantly increased plasma DMGV concentrations. DMGV is the product of metabolism of asymmetric dimethylarginine (ADMA) by the hepatic enzyme AGXT2. ADMA can also be metabolized to citrulline by the cytoplasmic enzyme DDAH1. We report that a high-sucrose diet induced conversion of ADMA exclusively into DMGV (supporting the relationship with sugary beverage intake in humans), while a high-fat diet promoted conversion of ADMA to both DMGV and citrulline. On the contrary, replacing dietary native starch with high-fiber-resistant starch increased ADMA concentrations and induced its conversion to citrulline, without altering DMGV concentrations. In a cohort of obese nondiabetic adults, circulating DMGV concentrations increased and ADMA levels decreased in those with either liver or muscle insulin resistance. This was similar to changes in DMGV and ADMA concentrations found in mice fed a high-sucrose diet. Sucrose is a disaccharide of glucose and fructose. Compared with glucose, incubation of hepatocytes with fructose significantly increased DMGV production. Overall, we provide a comprehensive picture of the dietary determinants of DMGV levels and association with insulin resistance.

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Fucoidan from sea cucumber protects against high-fat high-sucrose diet-induced hyperglycaemia and insulin resistance in mice

Journal of Functional Foods ◽

10.1016/j.jff.2014.05.012 ◽

2014 ◽

Vol 10 ◽

pp. 128-138 ◽

Cited By ~ 41

Author(s):

Shiwei Hu ◽

Guanghua Xia ◽

Jingfeng Wang ◽

Yuming Wang ◽

Zhaojie Li ◽

...

Keyword(s):

Insulin Resistance ◽

Sea Cucumber ◽

High Fat ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

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Long-term oral administration of osteocalcin induces insulin resistance in male mice fed a high-fat, high-sucrose diet

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00334.2015 ◽

2016 ◽

Vol 310 (8) ◽

pp. E662-E675 ◽

Cited By ~ 17

Author(s):

Yu Yasutake ◽

Akiko Mizokami ◽

Tomoyo Kawakubo-Yasukochi ◽

Sakura Chishaki ◽

Ichiro Takahashi ◽

...

Keyword(s):

Insulin Resistance ◽

Oral Administration ◽

Pancreatic Β Cell ◽

Male Mice ◽

High Fat ◽

Β Cell ◽

Sucrose Diet ◽

High Sucrose Diet ◽

High Sucrose

Uncarboxylated osteocalcin (GluOC), a bone-derived hormone, regulates energy metabolism by stimulating insulin secretion, pancreatic β-cell proliferation, and adiponectin expression in adipocytes. Previously, we showed that long-term intermittent or daily oral administration of GluOC reduced the fasting blood glucose level, improved glucose tolerance, and increased the fasting serum insulin concentration as well as pancreatic β-cell area in female mice fed a normal or high-fat, high-sucrose diet. We have now performed similar experiments with male mice and found that such GluOC administration induced glucose intolerance, insulin resistance, and adipocyte hypertrophy in those fed a high-fat, high-sucrose diet. In addition, GluOC increased the circulating concentration of testosterone and reduced that of adiponectin in such mice. These phenotypes were not observed in male mice fed a high-fat, high-sucrose diet after orchidectomy, but they were apparent in orchidectomized male mice or intact female mice that were fed such a diet and subjected to continuous testosterone supplementation. Our results thus reveal a sex difference in the effects of GluOC on glucose homeostasis. Given that oral administration of GluOC has been considered a potentially safe and convenient option for the treatment or prevention of metabolic disorders, this sex difference will need to be taken into account in further investigations.

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