Time-Restricted Feeding Restores Obesity-Induced Alteration in Adipose Tissue Immune Cell Phenotype

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.

Time-restricted feeding reduces monocyte production by controlling hematopoietic stem and progenitor cells in the bone marrow during obesity

“…In addition, TRF reduced mRNA expression of the transcription factor Cepba in BM cells. In summary, TRF is an effective dietary strategy to reduce overproduction of monocytes during obesity, which may be associated with the reduced CD11c + adipose tissue macrophages and insulin resistance seen in our previous study (22). LT-HSC, long-term hematopoietic stem cells; MPP, multipotent progenitors; Pre-GM, pre-granulocyte macrophage progenitors; GMP, granulocyte macrophage progenitors; LSK, Lin -Sca-1 + c-Kit + ; LK, Linc-Kit + cells; Lepr, leptin receptor; ↑H, increased by HFD ad libitum; ⨂, inhibited by TRF intervention.…”

“…Since ATM are associated with obesity-associated insulin resistance ( 11 , 54 – 56 ), reduced numbers of monocytes by TRF may result in fewer ATM and perhaps also with less proinflammatory profile for these ATM. Indeed, we previously reported that TRF intervention reduced numbers of total and proinflammatory ATM, along with the improvement of insulin resistance in overweight and obese mice ( 22 ). Real-time PCR of the total adipose tissue for the macrophage-associated genes Adgre1 (F4/80) and Itgax (CD11c) also indicated that TRF decreased proinflammatory ATM infiltration ( Figure 1M ), consistent with our previous findings ( 22 ) ( Figure 6 ).…”

“…Indeed, we previously reported that TRF intervention reduced numbers of total and proinflammatory ATM, along with the improvement of insulin resistance in overweight and obese mice ( 22 ). Real-time PCR of the total adipose tissue for the macrophage-associated genes Adgre1 (F4/80) and Itgax (CD11c) also indicated that TRF decreased proinflammatory ATM infiltration ( Figure 1M ), consistent with our previous findings ( 22 ) ( Figure 6 ). Thus, the regulation of monocyte pools by TRF may be a contributing factor to alleviated insulin resistance associated with obesity.…”

“…Previous studies in rodents and humans reported metabolic benefits of TRF, including reductions in body weight, adiposity, blood pressure, and/or insulin resistance (15)(16)(17)(18)(19)(20)(21). We recently demonstrated that TRF intervention reduced numbers of total and proinflammatory ATM, along with an improvement in glucose tolerance under high-fat diet (HFD) feeding (22). Although little is known about the effect of TRF on BM homeostasis under obesogenic conditions, a prior study has shown that lean mice with a fasting exhibit fewer monocytes in circulation by limiting egress from BM (23).…”

Time restricted feeding decreases renal innate immune cells and blood pressure in hypertensive mice

“…Additionally, they reported that fasting for as little as 4 h in mice significantly decreased macrophages in various tissues, however the kidneys were not examined. Lastly, Lee et al performed a study in which mice were fed a high fat diet for 8 weeks and some mice underwent a 14-h TRF [ 31 ]. They reported that TRF significantly decreased adipose tissue macrophages, which were CD45+CD11b+F4/80+, as well as CD11c+ macrophages, similar to our current findings of these same cells being decreased significantly in the kidneys of hypertensive mice that underwent a 12-h TRF for 4 weeks.…”