Sex-Specific Effects of High-fat Diet on Insulin Resis tanceand Anxiety-Like Behavior in Wis tar Rats

Objective: Peripheral metabolic disturbances are associatedwith an overall range of clinical health consequences such ashyperglycemia, hyperinsulinemia and hyperlipidemia, andcould contribute to the development of neuropsychiatric diseasesand anxiety-like behaviors. This study investigates whether۱۶-week high-fat diet (HFD) consumption causes insulin resistanceand anxiety-like behavior in a sex-dependent manner inrats when compared with normal chow diet (NCD) intake.Materials and Methods: After weaning, twenty male and femalerats were randomly fed HFD (۵۵.۹% fat) or NCD (۱۰%fat) for ۱۶-weeks. During the experiments, body weight, foodintake and calorie intake were recorded weekly. In the eighthweek of the study, animals’ blood samples were collectedthrough the retro-orbital sinus for measurement of glucose, insulin,and lipid profile. Also, at week ۸ and ۱۲ of the study, theglucose tolerance test was performed by intraperitoneal injectionof D-glucose and collecting blood via tail vein at ۰-, ۳۰-,۶۰-, and ۱۲۰-min intervals. Finally, anxiety-like behavior wasevaluated by elevated plus maze (EPM) test in the week ۱۶.Result: Despite a significant decrease in the cumulative weeklyfood intake, the gain in body weight and calorie intake werenot different in HFD compared to NCD treated rats in bothsexes. Glucose tolerance test results after ۸ weeks showed thatHFD significantly increased the blood glucose levels at ۳۰ and۶۰ min in male but not female HFD rats when compared withNCD groups. At week ۱۲, an increase in blood glucose levelsat ۳۰ min was observed in male but not female HFD rats whencompared to their respective control groups. The fasting bloodglucose and serum insulin were increased significantly in malebut not female HFD rats, therefore, male rats fed HFD showeda significant increase in the HOMA-IR index, an index of insulinresistance. The analysis of results related to lipid profilesshowed that the LDL-cholesterol concentration was remarkablyincreased in HFD rats compared to control group in both sexes.Evaluating anxiety-like behaviour showed that HFD rats spentsignificantly less time and fewer entries in the open arm of theEPM compared to rats fed the NCD in both sexes, indicatingincreased anxiety-like behaviour.Conclusions: Our results suggest that high-fat diet inducesperipheral insulin resistance in male rats, however, increasesanxiety-like behavior in both sexes.

کلیدواژه ها:

Anxiety-Like Behavior ، Metabolic Deficits ، Nutrition