The Onset of Steatosis Occurs as Early as Seven Days and Progresses to Non-Alcoholic Steatohepatitis in a Pediatric Pig Model of Non-Alcoholic Fatty Liver Disease.

Abstract

Background: Non-alcoholic fatty liver disease (NAFLD) is a chronic and progressive condition that afflicts patients of all ages, including neonates. Previously, we reported that neonatal pigs fed formulas rich in medium-chain (MCFA) compared with those fed long-chain fatty acid (LCFA) for 21 d, developed panacinar steatosis with no changes in whole body obesity.

Objectives: The objective of the present study was to examine the temporal onset and development of NAFLD in neonatal pigs in response to MCFA feeding.

Methods: Neonatal pigs (n=18) were fed isocaloric MCFA or LCFA. Six pigs from each group were euthanized following 7, 14 or 21 d of feeding. Body composition was assessed before initiation and at the end of the feeding period using dual-energy X-ray absorptiometry. Liver fat content and liver morphological features were determined from photomicrographs and evaluated for NAFLD by a pathologist.

Results: Lean mass and fat mass as a percentage of body weight were not different between formulas. However, liver weight (P = 0.001) and liver fat mass (P < 0.001) were greater for pigs in the MCFA compared with those in the LCFA group. Steatosis developed as early as 7 d in the MCFA compared with the LCFA fed pigs (P < 0.001). In addition, steatosis progressed in a portal to venous direction as MCFA feeding duration was increased (P = 0.02). Pigs diagnosed with NASH (P < 0.001) and greater non-alcoholic fatty liver disease scores were those in the MCFA group (P < 0.001).

Conclusions: These results suggest that the onset and progression of NAFLD from steatosis to NASH occurs rapidly in response to MCFA feeding. Moreover, periportal steatosis is the initial feature in the development of NAFLD before its progression to NASH. The development of NAFLD in neonates seems to occur independently of whole-body adiposity.