Implications of time-restricted feeding combined with resistance exercise or Reverb agonist on hepatic metabolism and circadian cycle in mice fed a high-fat diet

Abstract

Increased body adiposity is associated with hyperglycemia, contributing to an increased risk of developing type 2 diabetes mellitus (type 2 DM) in the obese population. In addition, studies show that high blood glucose levels and impaired insulin signaling are related to an exacerbated increase in hepatic glucose production. There is evidence that Krüppel-like transcription factor 15(KLF15) plays a crucial role in the process of gluconeogenesis and increased blood glucose. Thus, the addition of non-pharmacological strategies has also been indicated to combat the impacts of obesity on metabolic health. Time-restricted feeding (TRF) has shown the potential to decrease both body adiposity and hyperglycemia in preclinical models of high-fat diet-induced obesity. Some studies show that physical exercise may be a strategy capable of improving glycemic homeostasis and preventing the development of type 2 DM. However, the mechanisms linked to these effects achieved with these strategies have not been fully elucidated. In particular, there is still a considerable gap regarding the combined effect of TRF with resistance training exercises. Another relevant issue is related to poor diet and changes in the biological clock, with consequent disturbances in body metabolism, positive energy balance, and obesity. In this research proposal, we are proposing an intervention involving TRA combined with resistance physical exercise or administration of a Reverb protein agonist in mice fed a high-fat diet in the diurnal cycle. For this, mice will receive a high-fat diet for 8 weeks and will be submitted to TRA combined with resistance physical exercise or TRA combined with Reverb agonist administration. At the end of the experimental period, zoometric, physiological, histological, and molecular analyzes will be carried out. The findings may contribute to future actions to combat obesity and liver disorders as well as signal future therapeutic targets.