Time Restricted Feeding of a High Fat Diet protects against Adiposity, but not Liver Steatosis or increased Systemic TNF‐α levels
Authors: Crone Laura Brooks , Bloomer Richard , Butawan Matthew , Wyman Jacqueline , Hill Jessica Lynn , Liu Andrew , Lee Harold Weixiang , van der Merwe Marie 
Published: November 2023

Obesity and its associated low grade inflammation is a major risk factor for the development of many diseases including type 2 diabetes, nonalcoholic fatty liver disease, and cardiovascular disease. Time restricted feeding (TRF), in which food consumption is restricted to certain hours of the day, is a dietary approach that improves metabolic parameters when consuming a high fat diet. Many of the deleterious effects induced by this diet are propagated by changes in the circadian rhythm that in turn alters metabolic programs that regulate energy usage and storage. We therefore determined if timing of feeding would alter metabolic and inflammatory outcomes when following a time restricted feeding regimen. 9 week old C57/BL6 male mice were entrained to a reverse light‐dark cycle (12h light:12h dark), with lights off between the hours of 7 am‐7 pm, for 3 weeks. At 12 weeks of age, experimental mice were switched to a “Western‐type” high fat diet. (20% protein, 35% carbohydrate and 45% fat, mostly form lard). Mice had access to food ad libitum (HFL) or in a time restricted fashion during the dark (active) phase for 8 weeks. The TRF groups had access to food for 6 hours, either during the first half (TRF‐am: 7am–1pm) or second half (TRF‐pm: 1pm–7pm) of their active phase. Food consumption was monitored daily and body mass measured twice a week. Even though energy intake was slightly reduced only for the TRF‐am group (P<0.05), both TRF groups had greatly decreased total body weight gain (HFL: 16.43±1.86 g, TRF‐am: 5.61±2.6 g, TRF‐pm: 8.9±2.0) total body fat percentage (HFL: 17.78±2.20 g, TRF‐am: 9.76±3.65 g, TRF‐pm: 10.97±2.64), epididymal adipose tissue accumulation (HFL: 1.27±0.14 g, TRF‐am: 0.80±0.30 g, TRF‐pm: 0.95±0.21), and systemic leptin levels, with very little difference between TRF‐am and TRF‐ pm. Glucose tolerance and cholesterol levels were also improved with the restricted feeding, with TRF‐am demonstrating the greatest improvement in insulin sensitivity. However, there was severe liver steatosis and hypertrophy of adipocytes in the epididymal fat tissue of all groups, and, even though there was no difference in IL‐6 levels, systemic TNF‐α levels were increased in all groups consuming the high fat diet. The data presented here demonstrate that eating in a time restricted manner does protect against the development of excessive weight gain and adiposity, and that these outcomes were not different based on the timing of feeding. However, TRF did not prevent fat accumulation in the liver or the increase in systemic inflammatory molecules when consuming a high fat diet, suggesting that diet composition is the major contributor to these outcomes. These results suggest that time restricting the consumption of a high fat diet might be beneficial for weight loss, but the high fat nature of the diet is still able to induce physiological changes that will have negative health consequences. These results are of great importance for the design of dietary approaches for long term health benefits.

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