Intermittent Fasting Changes Your Fat Cells via VEGF

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Intermittent Fasting Changes Your Fat Cells via VEGF – Thomas DeLauer

Study – Cell Research

To minimize the differences in caloric intake which may be caused by the alternate day fasting, researchers developed a new IF regimen comprising 2 day feeding-1 day fasting periods

This regimen provided mice with sufficient time to compensate for the decreased body weight and for the reduced amount of food intake after 1-day fasting, to the level of non-fasted animals, enabling us to examine the effects of IF, independent of caloric intake difference

Results

Mice were subjected to 16 weeks of the 2:1 IF regimen on either normal chow diet (ND) or 45% high-fat diet (HFD). Compared to mice fed ad libitum/as desired (AL), IF mice showed lower body weight on both ND and HFD

IF and AL mice fed HFD (HFD-IF and HFD-AL) showed a marked difference in weight gain than those fed ND

Speculated that the reduced weight gain of IF animals might be due to the slight decrease in accumulated energy intake over 16 weeks of the diet program – however, the pair-feeding experiments consistently showed that IF animals exhibited reduced weight gain, compared to mice pair-fed ad libitum with exactly the same amount of food as IF mice

Body composition analysis revealed reduced fat mass without changes of lean mass in IF mice – consistently, HFD-IF mice exhibited a reduction in tissue weight and adipocyte size of both inguinal WAT (IWAT) and perigonadal WAT (PWAT) depots, compared to HFD-AL mice

Lipid accumulation in brown adipose tissue (BAT) was also decreased in HFD-IF, compared to HFD-AL mice

Notably, HFD-IF mice showed improved glucose homeostasis with smaller glucose excursion in glucose tolerance test (GTT), increased insulin sensitivity in insulin tolerance test (ITT), and markedly lower homeostasis model assessment-estimated insulin resistance (HOMA-IR), compared to HFD-AL or HFD-PF mice

IF mice exhibited lower liver weight, less lipid accumulation in liver, and lower plasma alanine aminotransferase (ALT) activity.

Together, the findings demonstrated that, in the absence of any energy intake difference, IF offers metabolic benefits against diet-induced obesity and metabolic dysfunction

BAT

Levels of beige/brown adipose markers were significantly elevated in PWAT of HFD-IF mice, compared to that of HFD-AL mice

Similar results were also observed in WAT of post HFD-IF mice. In addition, Ucp1 gene expression in BAT was found to be higher in HFD-IF mice compared to HFD-AL mice, suggesting increased BAT activation by IF

Suggests that IF led to an increase in beige adipocytes, thereby elevating energy expenditure, particularly during energy intake

Fasting Induces Browning of WAT via Adipose-VEGF Expression

Researchers next aimed to identify the molecular driver of IF-induced metabolic benefits and adipose thermogenesis – They found that fasting significantly increased VEGF expression in WAT

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They further examined how and where fasting-induced VEGF expression is regulated

VEGF expression levels in WAT increase progressively with the fasting duration and the increase can be immediately reversed by refeeding – Importantly, fasting-stimulated VEGF expression is restricted to WAT, not in BAT

**While previous studies have shown that sympathetic activity controls VEGF expression, total plasma catecholamine level was not increased by fasting, suggesting that fasting-stimulated VEGF expression in WAT is regulated via peripheral, not central, sympathetic nervous system**

Adipocytes are the major sources of fasting-mediated VEGF induction repeated fasting (i.e., IF) significantly increased WAT vascularization

Given that improved vascularization with adipose-derived VEGF plays a positive role in adipose tissue function and metabolic homeostasis against obesity and diabetes, our results together suggest that fasting-induced adipose VEGF expression underlies IF-induced metabolic benefits and adipose thermogenesis

*Also saw that the loss of adipose-VEGF abolished IF-mediated WAT browning*

*Fasting-induced adipose-VEGF induces M2 macrophage activation, which triggers WAT browning*

References

1) On-and-off fasting helps fight obesity, study finds: Researchers investigate why periods of sporadic fasting can be beneficial for the metabolism. (2018, September 19). Retrieved from https://www.sciencedaily.com/releases/2017/10/171017110041.htm

2) Intermittent fasting promotes adipose thermogenesis and metabolic homeostasis via VEGF-mediated alternative activation of macrophage. (2017, October 17). Retrieved from https://www.nature.com/articles/cr2017126

3) Role of Vascular Endothelial Growth Factor Signaling in Brown Adipocyte Survival, Proliferation and Function. (n.d.). Retrieved from https://dash.harvard.edu/handle/1/10417574