Differences in energy metabolism and mitochondrial redox status account for the differences in propensity for developing obesity in rats fed on high‐fat diet

Abstract

Obesity is a metabolic disease that is accompanied by oxidative stress. Mitochondrial dysfunction is closely associated with the occurrence and development of obesity. However, it is unclear if there are differences in mitochondrial redox homeostasis and energy metabolism between obesity‐prone (OP) and obesity‐resistant (OR) individuals and if these differences account for the different susceptibilities to developing obesity. The present study aimed to compare the regulation of energy metabolism between OP and OR rats during high‐fat diet (HFD)‐induced oxidative stress. Male Sprague Dawley rats were randomly divided into the control group and the HFD group. The HFD group was further divided into the OP and OR groups based on body weight gain (upper 1/3 for OP; lower 1/3 for OR) after eight weeks on HFD. Rats were sacrificed at the 8th and 20th week, and serum and organs were collected. At 8 weeks, HFD decreased mitochondrial antioxidant enzyme activity and increased the production of ROS in the OP rats, which was accompanied by unusual mitochondrial oxidative phosphorylation, reduced mitochondrial membrane potential (MMP), and decreased ATP production. When the feeding period was extended beyond the 8 weeks, the energy expenditure of the OP rats reduced further, resulting in elevated blood lipids and glucose levels and increased body weight. In contrast, the OR rats had higher mitochondrial antioxidant enzyme activity and normal redox homeostasis throughout the period, which was beneficial in energy utilization and ATP production. Thus, the increase in energy expenditure in the OR rats reduced the HFD‐induced weight gain. Mitochondrial function and antioxidant defense might be involved in the different propensities for developing obesity. Consequently, the ability of OR rats to resist obesity may be attributed to their ability to maintain mitochondrial function and redox balance.

Intergenerational effects of preconception opioids on glucose homeostasis and hepatic transcription in adult male rats

“…Non-alcoholic fatty liver disease , oxidative phosphorylation, diabetic cardiomyopathy, Alzheimer’s disease ; see Supplemental File 3 ). This suggests that F0 adolescent morphine exposure, even under CD conditions, results in alterations in hepatic transcription consistent with the effects of FSD maintenance 28 . Moreover, many of the pathways identified implicate metabolic and inflammatory processes that are frequently associated with negative health outcomes.…”

“…Indeed, Lu et al, recently reported that 8 weeks of high fat diet (HFD) feeding resulted in impaired mitochondrial respiratory function concurrent with dyslipidemia that worsened as the feeding period was extended. Further, while HFD fed males maintained normal glycemia following the 8-week feeding paradigm, prolonged feeding (20 weeks) was sufficient to induce hyperglycemia 28 .…”

Resistance to obesity prevents obesity development without increasing spontaneous physical activity and not directly related to greater metabolic and oxidative capacity

“…Study groups have worked with the hypothesis that OR is due to a complex interaction of several metabolic factors that are activated to a greater or lesser extent in response to environmental factors, for example, contact and maintenance of a high-fat diet [ 9 , 32 , 33 ]. In this sense, researchers have invested efforts in mapping biomarkers of energy production, storage and consumption systems [ 2 , 4 , 9 , 24 , 29 , 34 ].…”

“…However, the etiology of OR is still unknown in the literature, since its characterization was described more than three decades ago. In this sense, most of the works dedicate efforts to the study of metabolism and metabolic pathways related to the accumulation and/or oxidation of adipose tissue alone [ 2 – 4 ] or associated with spontaneous physical activity [ 5 – 7 ], but the study of lipid oxidation pathways in skeletal muscles in models of OR still seem to be scarce.…”

Comparison of Visceral Fat Lipolysis Adaptation to High-Intensity Interval Training in Obesity-Prone and Obesity-Resistant Rats

“…Similarly to the heterogeneity of human obesity, rodents also show two different obesity phenotypes, namely OP and OR 14,15 . Although the baseline weights of these rats are the same, marked differences in food intake, PA, central regulation and peripheral tissue metabolism lead OP rats to become obese after several weeks of receiving a HFD, while OR rats tend to remain at a normal weight [32][33][34] . We established a model of OP and OR rats by using a classic programme involving a HFD 14,15,34 .…”