Depot-Dependent Impact of Time-Restricted Feeding on Adipose Tissue Metabolism in High Fat Diet-Induced Obese Male Mice

Abstract

Time-restricted feeding (TRF) is known to be an effective strategy for weight loss and metabolic health. TRF’s effect on metabolism is complex and likely acts on various pathways within multiple tissues. Adipose tissue plays a key role in systemic homeostasis of glucose and lipid metabolism. Adipose tissue dysregulation has been causally associated with metabolic disorders in obesity. However, it is largely unknown how TRF impacts metabolic pathways such as lipolysis, lipogenesis, and thermogenesis within different in adipose tissue depots in obesity. To determine this, we conducted a 10-week TRF regimen in male mice, previously on a long-term high fat diet (HFD) and subjected the mice to TRF of a HFD for 10 h per day or ad libitum. The TRF regimen showed reduction in weight gain. TRF restored HFD-induced impairment of adipogenesis and increased lipid storage in white adipose tissues. TRF also showed a depot-dependent effect in lipid metabolism and restored ATP-consuming futile cycle of lipogenesis and lipolysis that is impaired by HFD within epididymal adipose tissue, but not inguinal fat depot. We demonstrate that TRF may be a beneficial option as a dietary and lifestyle intervention in lowering bodyweight and improving adipose tissue metabolism.

Effect of Aerobic Exercise and Time‐Restricted Feeding on Metabolic Markers and Circadian Rhythm in Mice Fed with the High‐Fat Diet

“…The different results could be due to time of animal sacrifice at ZT0.5 (within 30 min of lights on) since Rev-Erb𝛼 expressions is lowest in the morning and peaks during start of the dark phase in peripheral tissues. [78] PGC-1𝛼 regulates many metabolic processes including mitochondrial biogenesis, hepatic gluconeogenesis, and thermogenesis. [79,80] In our study, PGC-1𝛼 increased with tRF, exercise, and tRF-Ex in the liver.…”

Time‐restricted feeding regulates lipid metabolism under metabolic challenges

“…Upon evaluation of recent studies, there are similarities in the observations regarding the effects of TRF on lipid levels and metabolism. Firstly, TRF may reduce the incidences of insulin resistance [21,[24][25][26] with the majority of these studies performed in high-fat diet or obese conditions in mice and fruit flies. Furthermore, TRF increases the overall expression of genes related to FA synthesis and oxidation, with increased expression amplitude on FA synthesis genes in WAT and FA oxidation in BAT (Figure 1).…”

“…[13] In brown adipose tissue (BAT), TRF increases expression of genes involved in FA synthesis and oxidation, and rhythmicity of FA oxidation with peak expression during fasting period. [13,18] In liver, TRF increases the rhythmicity of genes associated with FA synthesis and oxidation. While reduced mesor expression with peak expression during feeding was observed for the genes associated with FA synthesis, increased mesor expression with peak expression during fasting was observed for the genes associated with FA oxidation.…”

“…Multiple studies have also investigated gene expression of lipid metabolism, however, at a select time point or after an extended fasting period. For example, Bushman et al study [18] evaluated lipid metabolism gene expression after a 10-week 14:10 TRF. They found that TRF increased the expressions of genes involved in lipolysis and lipogenesis, and reduced expressions of genes associated with FA oxidation in both BAT and eWAT, while iWAT did not follow a consistent trend in those gene expressions.…”

“…The beneficial effects of TRF on the adipose tissue has been observed by numerous studies to date. In a recent study of Bushman et al., [ 18 ] 10 weeks of a 14:10 TRF regimen conducted in male mice under HFD displayed an increase in size of adipose cells in both iWAT and eWAT compared to a normal chow diet, suggesting TRF restores adipogenesis and lipid storage capacity. On the other hand, in BAT, while H&E staining showed an increase in the size of adipocyte under HFD, TRF induced a reduction of adipocyte size, suggesting that TRF reverses HFD‐induced whitening of BAT.…”