Abstract

Studies suggest that time-restricted feeding (TRF) may prevent obesity and its commodities. At present, little is known about how TRF impacts immune cells, and whether such an effect is linked to altered metabolic parameters under condition of a high-fat diet (HFD)-induced obesity. To address these issues, we conducted a study in which we determined whether TRF has therapeutic efficacy against weight gain, adiposity, as well as associated immune cell disturbance found in obese mice. Six-week-old male C57BL/6 mice were fed a low-fat diet (LFD) or HFD ad libitum for six weeks, after which time a subgroup of HFD mice was switched to the 10 h TRF paradigm (HFD-TRF) for additional eight weeks. We found that TRF intervention reduced HFD-induced weight gain. Even with comparable fat mass and mean adipocyte area, the HFD-TRF group had lower mRNA levels of proinflammatory cytokine Tnfα and chemokine Ccl8, along with reduced numbers of adipose tissue macrophages (ATM), CD11c+ ATM, and CD8+ T cell compared to the HFD group, while maintaining CD8+ to CD4+ ratio at levels similar to those in the LFD group. Furthermore, TRF intervention was effective in improving glucose tolerance and reducing HOMA-IR. Taken together, our findings suggest that TRF restores the obesity-induced alteration in immune cell composition, and this effect may in part contribute to health benefits (including insulin sensitivity) of practicing TRF.

Highlights

  • Time-restricted feeding (TRF) is a particular form of intermittent fasting, which is mainly characterized by limiting the time window of energy intake within a few hours every day without an overt attempt at modification [1]

  • We found that Efficiency Ratio (EER) was significantly higher in the high-fat diet (HFD) group compared to the low-fat diet (LFD) group, while mice in the HFD-time-restricted feeding (TRF) group exhibited EER values similar to those in the LFD group

  • These results indicate that TRF intervention may have metabolic benefits beyond controlling dietary intake (Table 1)

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Summary

Introduction

Time-restricted feeding (TRF) is a particular form of intermittent fasting, which is mainly characterized by limiting the time window of energy intake within a few hours every day without an overt attempt at modification [1] Compared with those with ad libitum access to a high-fat diet, mice that were subjected to daily TRF (8–15 h) during the active phase are largely protected from excessive body weight gain, adiposity, and/or insulin resistance under high-fat diet feeding and other nutritional challenges [2,3,4,5]. CD8 depletion using neutralizing antibody was shown to ameliorate pre-established obese adipose inflammation and glucose intolerance [18]. These results indicate that obesity modulates immune cell phenotype, which in turn contributes to the pathogenesis of obesity-related insulin resistance

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