Sex Differences in High Fat Diet‐Induced Enhanced Sensitivity to the Locomotor Stimulating Effects of Methamphetamine and SKF 82958

Excessive dietary fat intake is related to metabolic dysfunction and enhances susceptibility to hypertension and cognitive impairment. Although there are sex differences in the prevalence and progression of these diseases, few studies have investigated sex differences in cardio-metabolic and cognitive parameters in rats with high-fat diet-induced metabolic dysfunction. To better reflect actual clinical conditions, sex-differences in rats with high-fat diet-induced metabolic dysfunction were evaluated. Male and female Sprague-Dawley rats were fed a high-fat diet to induce metabolic dysfunction and intraperitoneally injected with N-nitro-L-arginine methyl ester and scopolamine to model vulnerability to hypertension and cognitive impairment, respectively, whereas control rats were fed a regular diet and treated with distilled water and 0.9% saline. Male experimental rats showed significantly higher systolic blood pressure than female experimental animals. More importantly, acetylcholine-induced relaxation of carotid arteries was decreased only in the male experimental rats, revealing a significant difference compared with female experimental rats. These findings provide evidence for individualized sex-based management of patients with metabolic dysfunction and susceptibilities to hypertension and cognitive impairment. Impact statement Excessive dietary fat intake plays important roles in the process of metabolic dysfunction and increases susceptibilities to chronic diseases such as hypertension. Few previous studies, however, have accurately reflected real-world medical conditions. In addition, studies performed to date have not examined detailed sex-differences in cardio-metabolic and cognitive parameters, precluding the development of sex-tailored interventions for patients with metabolic dysfunction who are susceptible to hypertension and cognitive impairment. In this study, using rats with HFD-induced metabolic dysfunction that made them susceptible to hypertension and cognitive impairment, we demonstrate that male rats show greater impairment of acetylcholine-induced vasorelaxation of the carotid artery and systolic blood pressure compared to female rats. These findings may provide a basis for the early detection of carotid artery dysfunction and systolic blood pressure increase, especially in males.

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SIM1 Overexpression Partially Rescues Agouti Yellow and Diet-Induced Obesity by Normalizing Food Intake

Endocrinology ◽

10.1210/en.2006-0453 ◽

2006 ◽

Vol 147 (10) ◽

pp. 4542-4549 ◽

Cited By ~ 54

Author(s):

Bassil M. Kublaoui ◽

J. Lloyd Holder ◽

Kristen P. Tolson ◽

Terry Gemelli ◽

Andrew R. Zinn

Keyword(s):

Food Intake ◽

Energy Expenditure ◽

Transgenic Mice ◽

High Fat Diet ◽

Chow Diet ◽

High Fat ◽

Enhanced Sensitivity ◽

Diet Induced Obesity ◽

Melanocortin 4 Receptor ◽

Obesity In Mice

Single-minded 1 (SIM1) mutations are associated with obesity in mice and humans. Haploinsufficiency of mouse Sim1 causes hyperphagic obesity with increased linear growth and enhanced sensitivity to a high-fat diet, a phenotype similar to that of agouti yellow and melanocortin 4 receptor knockout mice. To investigate the effects of increased Sim1 dosage, we generated transgenic mice that overexpress human SIM1 and examined their phenotype. Compared with wild-type mice, SIM1 transgenic mice had no obvious phenotype on a low-fat chow diet but were resistant to diet-induced obesity on a high-fat diet due to reduced food intake with no change in energy expenditure. The SIM1 transgene also completely rescued the hyperphagia and partially rescued the obesity of agouti yellow mice, in which melanocortin signaling is abrogated. Our results indicate that the melanocortin 4 receptor signals through Sim1 or its transcriptional targets in controlling food intake but not energy expenditure.

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Intermittent dietary fish oil supplementation prevents high fat diet‐induced enhanced sensitivity to the behavioral effects of quinpirole

The FASEB Journal ◽

10.1096/fasebj.2019.33.1_supplement.805.2 ◽

2019 ◽

Vol 33 (S1) ◽

Author(s):

Nina M Beltran ◽

Kayla I Galindo ◽

Jose Echeverri ◽

Caroline Hernandez‐Casner ◽

Katherine M Serafine

Keyword(s):

Fish Oil ◽

High Fat Diet ◽

Behavioral Effects ◽

High Fat ◽

Enhanced Sensitivity ◽

Dietary Fish ◽

Fish Oil Supplementation

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Sex Differences in Metabolic Recuperation After Weight Loss in High Fat Diet-Induced Obese Mice

Frontiers in Endocrinology ◽

10.3389/fendo.2021.796661 ◽

2021 ◽

Vol 12 ◽

Author(s):

Santiago Guerra-Cantera ◽

Laura M. Frago ◽

Roberto Collado-Pérez ◽

Sandra Canelles ◽

Purificación Ros ◽

...

Keyword(s):

Weight Loss ◽

Sex Differences ◽

Glucose Metabolism ◽

High Fat Diet ◽

Dietary Intervention ◽

Mrna Levels ◽

High Fat ◽

Obesity Epidemic ◽

Igf System ◽

Males And Females

Dietary intervention is a common tactic employed to curtail the current obesity epidemic. Changes in nutritional status alter metabolic hormones such as insulin or leptin, as well as the insulin-like growth factor (IGF) system, but little is known about restoration of these parameters after weight loss in obese subjects and if this differs between the sexes, especially regarding the IGF system. Here male and female mice received a high fat diet (HFD) or chow for 8 weeks, then half of the HFD mice were changed to chow (HFDCH) for 4 weeks. Both sexes gained weight (p < 0.001) and increased their energy intake (p < 0.001) and basal glycemia (p < 0.5) on the HFD, with these parameters normalizing after switching to chow but at different rates in males and females. In both sexes HFD decreased hypothalamic NPY and AgRP (p < 0.001) and increased POMC (p < 0.001) mRNA levels, with all normalizing in HFDCH mice, whereas the HFD-induced decrease in ObR did not normalize (p < 0.05). All HFD mice had abnormal glucose tolerance tests (p < 0.001), with males clearly more affected, that normalized when returned to chow. HFD increased insulin levels and HOMA index (p < 0.01) in both sexes, but only HFDCH males normalized this parameter. Returning to chow normalized the HFD-induced increase in circulating leptin (p < 0.001), total IGF1 (p < 0.001), IGF2 (p < 0.001, only in females) and IGFBP3 (p < 0.001), whereas free IGF1 levels remained elevated (p < 0.01). In males IGFBP2 decreased with HFD and normalized with chow (p < 0.001), with no changes in females. Although returning to a healthy diet improved of most metabolic parameters analyzed, fIGF1 levels remained elevated and hypothalamic ObR decreased in both sexes. Moreover, there was sex differences in both the response to HFD and the switch to chow including circulating levels of IGF2 and IGFBP2, factors previously reported to be involved in glucose metabolism. Indeed, glucose metabolism was also differentially modified in males and females, suggesting that these observations could be related.

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