Dietary macronutrients and the aging liver sinusoidal endothelial cell
Victoria Carroll Cogger, Mashani Mohamad, Samantha Marie Solon-Biet, Alistair M. Senior, Alessandra Warren, Jennifer Nicole O'Reilly, Bui Thanh Tung, Dmitri Svistounov, Aisling Clare McMahon, Robin Fraser, David Raubenheimer, Andrew J. Holmes
American Journal of Physiology. Heart and Circulatory Physiology
Fenestrations are pores within the liver sinusoidal endothelial cells (LSECs) that line the sinusoids of the highly vascularized liver. Fenestrations facilitate the transfer of substrates between blood and hepatocytes. With pseudocapillarization of the hepatic sinusoid in old age, there is a loss of fenestrations. LSECs are uniquely exposed to gut-derived dietary and microbial substrates delivered by the portal circulation to the liver. Here we studied the effect of 25 diets varying in content
... f macronutrients and energy on LSEC fenestrations using the Geometric Framework method in a large cohort of mice aged 15 mo. Macronutrient distribution rather than total food or energy intake was associated with changes in fenestrations. Porosity and frequency were inversely associated with dietary fat intake, while fenestration diameter was inversely associated with protein or carbohydrate intake. Fenestrations were also linked to diet-induced changes in gut microbiome, with increased fenestrations associated with higher abundance of Firmicutes and reduced abundance of Bacteroidetes. Diet-induced changes in levels of several fatty acids (C16:0, C19:0, and C20:4) were also significantly inversely associated with fenestrations, suggesting a link between dietary fat and modulation of lipid rafts in the LSECs. Diet influences fenestrations and these data reflect both the key role of the LSECs in clearing gut-derived molecules from the vascular circulation and the impact these molecules have on LSEC morphology. aging; fenestrations; microbiome NEW & NOTEWORTHY We demonstrate a link among diet, the gut microbiome, and fenestrations of the liver sinusoidal endothelium. Fenestrations are reorganized in response to diet, potentially in conjunction with the composition and activity of the gut microbiome. The effects of diet and microbiome on the fenestrations have significant implications for liver function into old age.