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

Ravi Yadav; Samuel D Gerrard; Marta R M Lima; Teresa L Southard; Nishanth E Sunny; Samer W El-Kadi

doi:10.1016/j.tjnut.2024.11.009

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

J Nutr. 2024 Nov 12:S0022-3166(24)01176-3. doi: 10.1016/j.tjnut.2024.11.009. Online ahead of print.

Authors

Ravi Yadav¹, Samuel D Gerrard¹, Marta R M Lima¹, Teresa L Southard², Nishanth E Sunny³, Samer W El-Kadi⁴

Affiliations

¹ School of Animal Sciences, Virginia Tech, Blacksburg, VA, United States.
² Virginia-Maryland College of Veterinary Medicine, Virginia Tech, Blacksburg, VA, United States.
³ Department of Animal and Avian Sciences, University of Maryland, MD, United States.
⁴ School of Animal Sciences, Virginia Tech, Blacksburg, VA, United States. Electronic address: [email protected].

PMID: 39536967
DOI: 10.1016/j.tjnut.2024.11.009

Abstract

Background: Nonalcoholic 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 formulas rich in long-chain fatty acid (LCFA) for 21 d, developed panacinar steatosis with no changes in whole-body adiposity.

Objectives: The objective of this 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 formulas. Six pigs from each group were killed 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 morphologic 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 than those for pigs 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 increased (P = 0.02). Pigs diagnosed with NASH (P < 0.001) and greater nonalcoholic 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 nonalcoholic steatohepatitis occurs rapidly in response to MCFA feeding. Moreover, periportal steatosis is the initial feature in the development of NAFLD before its progression to nonalcoholic steatohepatitis. The development of NAFLD in neonates seems to occur independently of whole-body adiposity.

Keywords: NAFLD activity score (NAS); hepatic steatosis; long-chain fatty acids; medium-chain fatty acids; neonatal pig model; nonalcoholic fatty liver disease (NAFLD); nonalcoholic steatohepatitis (NASH).