Peer Review #1 of "Impact of body weight gain on hepatic metabolism and hepatic inflammatory cytokines in comparison of Shetland pony geldings and Warmblood horse geldings (v0.1)"

Abstract

Background. Non-alcoholic fatty liver disease is known as determining part of human obesity. The impact of body weight (BW) gain on liver metabolism has not been extensively investigated yet. Objectives. To investigate hepatic alterations caused by increasing BW in ponies and horses. Animals. 19 non-obese equines (10 Shetland ponies, geldings; nine Warmblood horses, geldings). Methods. Animals received 200% of their metabolizable maintenance energy requirements for two years. Serum alkaline phosphatase (ALP), glutamate dehydrogenase (GLDH), aspartate aminotransferase (AST), and gamma-glutamyl transferase (GGT) activities and bile acids (BA) were analyzed several times during two years of hypercaloric diet. Hepatic lipid content and hepatic levels of the interleukin (IL)-6, tumor necrosis factor α (TNFα), cluster of differentiation (CD) 68, IL-1β, lipoprotein lipase (LPL), fatty acidbinding protein 1 (FABP1), chemerin and nuclear factor κ B (NF-κB) mRNAs were assessed at the start of the study and after one and two years of excess energy intake. Results. The mean (± SD) BW gain recorded during two years of excess energy intake was 29.9 ± 19.4% for ponies and 17 ± 6.74% for horses. The hepatic lipid content was not profoundly affected by increasing BW. Levels of the IL-6, TNFα, CD68 and IL-1β mRNAs did not change during BW gain. Levels of the chemerin mRNA increased significantly in both breeds (ponies: P = 0.02; horses: P = 0.02) in response to BW gain. Significant differences in serum GLDH and AST activities, serum bile acid concentrations and hepatic levels of the LPL mRNA were observed between ponies and horses at the end of the study. Conclusions: Chemerin might represent an interesting marker for future equine obesity research. Interestingly, steatosis caused by increasing BW may occur later in the development of obesity in equines than in humans. Additionally, the hepatic metabolism exhibits differences between ponies and horses, which may explain in part the greater susceptibility of ponies to obesity-associated metabolic dysregulations.