Dietary macronutrients and the aging liver sinusoidal endothelial cell

Abstract

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 of 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.

Current Knowledge about the Effect of Nutritional Status, Supplemented Nutrition Diet, and Gut Microbiota on Hepatic Ischemia-Reperfusion and Regeneration in Liver Surgery

“…Evidence points to the involvement of the gut microbiota in the pathogenesis of NAFLD [130,131]. Cogger et al showed that liver sinusoidal endothelial cells (LSECs) fenestrae are inversely and positively correlated with the gut abundance of Bacteroidetes and Firmicutes, respectively [132]. The gut microbiota also has an emerging role in NASH as a source of inflammatory stimuli [130,133].…”

Novel targets for delaying aging: The importance of the liver and advances in drug delivery

“…This im pairs detox i fi ca tion and clear ance of var i ous en do bi otics (e.g. lipopro teins and in sulin) [94] and xeno biotics (e.g. drugs, neu ro tox ins and car cino gens) [95].…”

“…The re duc tion in blood flow to the liver re flects a gen eral down reg u la tion of splanch nic blood flow in all ab dom i nal or gans rather than any spe cific he patic ef fects on vascu lar re sis tance. The re duc tion in the trans fer of sub strates be tween blood and he pa to cytes oc curs mainly as a re sult of the loss of fen estra tions as so ci ated with pseudo cap il lar iza tion [2,24,25,94,95,99]. All these ag ing liver changes will im pact on the re spon sive ness and activ ity of the nu tri ent sens ing path ways.…”

Nutritional strategies to optimise cognitive function in the aging brain

“…LPHC diets were found to inhibit hepatic mTOR, providing a mechanism linking this type of ad libitum diet to delayed aging. GF was utilized to unravel the complex effects of macronutrients on metabolic health, lifespan (Solon-Biet et al, 2014), immunity (Le Couteur et al, 2015), reproduction (Solon-Biet et al, 2015b) and microcirculation (Cogger et al, 2016). GF methodology is therefore likely to provide insight into how dietary energy and macronutrients influence brain aging and dementia.…”