Time-restricted feeding mice a high-fat diet induces a unique lipidomic profile

Authors: Mehus, Aaron; Rust, Bret; Idso, Joseph; Hanson, Benjamin; Zeng, Huawei; Yan, Lin; Bukowski, Michael; Picklo, Matthew

Submitted to: Journal of Nutritional Biochemistry
Publication Type: Peer Reviewed Journal
Publication Acceptance Date: 10/18/2020
Publication Date: 10/22/2020
Citation: Mehus, A.A., Rust, B.M., Idso, J.P., Hanson, B.K., Zeng, H., Yan, L., Bukowski, M.R., Picklo, M.J. 2020. Time-restricted feeding mice a high-fat diet induces a unique lipidomic profile. Journal of Nutritional Biochemistry. 88. Article 108531. https://doi.org/10.1016/j.jnutbio.2020.108531.
DOI: https://doi.org/10.1016/j.jnutbio.2020.108531

Interpretive Summary: Time restricted feeding (TRF; also known as intermittent fasting) has gained attention as a potential way to reduce body fat gain and to reduce health problems like insulin resistance and fatty liver. In mice, eating a diet high in fat throughout the day leads to obesity, insulin resistance, and fatty liver. However, this intake of a high fat diet also leads to increases in long chain polyunsaturated fatty acids (LCPUFA), that are considered to be beneficial for health. In this work, we (1) tested the hypothesis that TRF of a high-fat diet maintains elevated LCPUFA indices while preventing insulin resistance and fatty liver and (2) determined the impact of TRF upon fat metabolism in mice. Our data show that, in mice, TRF of a high fat diet blocks fatty liver and insulin resistance but does elevate LCPUFA content in the liver and plasma. On the other hand, TRF creates a separate, unique profile for fat metabolism in mice indicative of positive adaptations following HF intake in this time restricted, intermittent fasting-type manner. These findings are of clinical and nutritional interest.

Technical Abstract: Time-restricted feeding (TRF) can reduce adiposity and lessen the co-morbidities of obesity. Mice consuming obesogenic high-fat (HF) diets develop insulin resistance and hepatic steatosis, but have elevated indices of long-chain polyunsaturated fatty acids (LCPUFA) that may be beneficial. While TRF impacts lipid metabolism, scant data exist regarding the impact of TRF upon lipidomic composition of tissues. We (1) tested the hypothesis that TRF of a HF diet maintains elevated LCPUFA indices while preventing insulin resistance and hepatic steatosis and (2) determined the impact of TRF upon the lipidome in plasma, liver, and adipose tissue. Male, adult mice were fed a control, diet ad libitum, a HF diet ad libitum (HF-AL), or a HF diet with TRF for 12 hours during the dark phase (HF-TRF). HF-TRF prevented insulin resistance and hepatic steatosis resulting from by HF-AL treatment. TRF blocked plasma increases in LCPUFA induced by HF-AL treatment but elevated concentrations of triacylglycerols (TAG) and non-esterified saturated fatty acids. Analysis of the hepatic lipidome demonstrated that TRF did not elevate LCPUFA while reducing steatosis. However, TRF created (1) a separate hepatic lipid signature for TAG, phosphatidylcholine, and phosphatidylethanolamine species and (2) modified gene and protein expression consistent with reduced fatty acid synthesis and restoration of diurnal gene signaling. TRF increased the saturated fatty acid content in visceral adipose tissue. In summary, TRF of a HF diet alters the lipidomic profile of plasma, liver, and adipose tissue, leading to a third distinct lipid metabolic state indicative of positive metabolic adaptations following HF intake.