Dietary Long-Chain Fatty Acids Accelerate Metabolic Dysfunction in Guinea Pigs with Non-Alcoholic Steatohepatitis

Abstract

The composition of dietary fatty acids may be important for the development and progression of metabolic syndrome and non-alcoholic steatohepatitis (NASH). This study investigated the effect of two high-fat diets based on coconut oil, containing predominantly medium-chain fatty acids (MCFA), or cocoa butter, containing mainly long-chain fatty acids (LCFA), on glucose homeostasis and NASH in guinea pigs following 16 and 32 weeks of diet. At week 16, glucose intolerance was increased in the LCFA animals compared to the MCFA animals (p < 0.001), with both groups differing from the controls by week 32 (p < 0.0001), supported by increased hemoglobin A1c (p < 0.05). NASH was present in both high-fat groups from week 16, with advancing fibrosis appearing more progressive in the LCFA animals at week 16. In agreement, gene expression showed overall increased expression of NASH target genes in the LCFA animals compared to the MCFA animals at weeks 16 and 32 (p < 0.05 and p < 0.0001, respectively). The LCFA animals also displayed increased plasma uric acid at both time points (p < 0.05), a phenomenon linked to NASH in humans. In conclusion, this study reports that a diet high in LCFA promotes metabolic imbalance and may accelerate NASH-associated hepatic fibrosis. This highlights the importance of a critical evaluation of fatty acid composition when investigating NASH-associated endpoints.

Probiotic Limosilactobacillus reuteri DSM 17938 Changes Foxp3 Deficiency-Induced Dyslipidemia and Chronic Hepatitis in Mice

“…The elevation of sphingolipids, including ceramide, described in SLE and RA, can lead to apoptosis, endothelial dysfunction, and perpetuation of autoimmunity [ 61 ]; hence, a similar mechanism may be postulated in Treg-associated autoimmune pathogenesis. It is noteworthy that a diet rich in LCFAs can contribute to nonalcoholic steatohepatitis development in human and guinea pig models [ 62 ]. Despite elevated LCFAs in SF mice, liver histology did not show signs of steatosis, indicating that LCFAs may contribute to hepatitis by exaggerating T helper immune responses rather than causing steatohepatitis.…”