Sexual dimorphism in cardiometabolic and cardiac mitochondrial function in obese rats following sex hormone deprivation

Abstract

Objective: Our study aims to test the hypothesis that poorer function of cardiac mitochondria in males, under sex hormone-deprived and obese-insulin-resistant conditions, is responsible for a worse cardiometabolic function than females. Methods: One hundred and forty-four rats were subjected to receive either 12 weeks of normal diet (ND) or a high-fat diet (HFD) consumption following the induction of sex hormone deprivation. Temporal evaluations of metabolic parameters, cardiac autonomic modulation, left ventricular (LV) contractile, and mitochondrial functions were measured after starting each feeding protocol for 4, 8, and 12 weeks. Results: After HFD feeding for 8 weeks, increased plasma insulin and HOMA index were initially observed in male HFD-fed sham-operated rats (M-HFS), male HFD-fed orchiectomized rats (M-HFO), female ND-fed ovariectomized rats (F-OVX), female HFD-fed sham-operated rats (F-HFS), and female HFD-fed ovariectomized rats (F-HFO) groups. In addition, as early as week 4, male ND-fed orchiectomized rats (M-ORX) and M-HFO exhibited impaired cardiac autonomic balance, LV contractile and mitochondrial functions, whereas M-HFS and F-HFO developed these impairments at week 8 and F-OVX and F-HFS exhibited them at week 12. Conclusion: We concluded that sex hormone-deprived females are prone to develop metabolic impairments, whereas males are more likely to have cardiac autonomic impairment, LV contractile and mitochondrial dysfunction even in the absence of obese-insulin-resistant condition. However, under estrogen-deprived condition, these impairments were further accelerated and aggravated by obese-insulin resistance.