Age and sex as confounding factors in the relationship between cardiac mitochondrial function and type 2 diabetes in the Nile Grass rat

Abstract

Our study revisits the role of cardiac mitochondrial adjustments during the progression of type 2 diabetes mellitus (T2DM), while considering age and sex as potential confounding factors. We used the Nile Grass rats (NRs) as the animal model. After weaning, animals were fed either a Standard Rodent Chow Diet (SRCD group) or a Mazuri Chinchilla Diet (MCD group) consisting of high-fiber and low-fat content. Both males and females in the SRCD group, exhibited increased body mass, body mass index, and plasma insulin compared to the MCD group animals. However, the females were able to preserve their fasting blood glucose throughout the age range on both diets, while the males showed significant hyperglycemia starting at 6 months in the SRCD group. In the males, a higher citrate synthase activity-a marker of mitochondrial content-was measured at 2 months in the SRCD compared to the MCD group, and this was followed by a decline with age in the SRCD group only. In contrast, females preserved their mitochondrial content throughout the age range. In the males exclusively, the complex IV capacity expressed independently of mitochondrial content varied with age in a diet-specific pattern; the capacity was elevated at 2 months in the SRCD group, and at 6 months in the MCD group. In addition, females, but not males, were able to adjust their capacity to oxidize long-chain fatty acid in accordance with the fat content of the diet. Our results show clear sexual dimorphism in the variation of mitochondrial content and oxidative phosphorylation capacity with diet and age. The SRCD not only leads to T2DM but also exacerbates age-related cardiac mitochondrial defects. These observations, specific to male NRs, might reflect deleterious dietary-induced changes on their metabolism making them more prone to the cardiovascular consequences of aging and T2DM.

Early Time-Restricted Feeding Amends Circadian Clock Function and Improves Metabolic Health in Male and Female Nile Grass Rats

“…The higher concentrations of hepatic triglycerides and fatty acids and the lower amount of adipose tissue measured in females than males suggest sexual dimorphism in hepatic metabolism and fat distribution between the male and female rats profiled in this study. Similarly, Schneider et al demonstrated sex-dependent differences in Nile grass rats with respect to cardiac function [45]. Moreover, in a nocturnal rodent model, the weight benefits associated with TRF were sex-dependent and observed in male mice only [46].…”

Multi-Tissue Time-Domain NMR Metabolomics Investigation of Time-Restricted Feeding in Male and Female Nile Grass Rats

“…In this study, Nile grass rats (NGR) were selected as the model animal as they are diurnal and have circadian regulation that is similar to humans. They also develop the constellation of MetS symptoms solely through dietary manipulation (no genetic or chemical alterations) and mimic much of the disease progression observed in humans [ 43 , 44 , 45 ].…”

Plasma acylcarnitine and diabetic retinopathy: A study from Eastern China

“…Therefore, the accumulations of long-chain ACars in plasma are often used to suggest defective FAO. Although there is no direct evidence that long-chain ACars are harmful to DR, a previous study has suggested that the inability of patients to regulate the oxidation of long-chain fatty acids will make them more susceptible to oxidative stress ( 28 ), which further increases the risk of developing DR ( 29 ). Therefore, this may be a potential interpretation of why high levels of long-chain ACars in plasma are associated with DR, while medium-chain ACars showed negative associations.…”