The distinct hepatic metabolic profiles and the relations with impaired liver function in congenital isolated growth hormone deficient rats.

OBJECTIVE: Patients with growth hormone deficiency (GHD) with inadequate growth hormone levels are often correlated with nonalcoholic fatty liver disease (NAFLD). However, potential mechanism of how GHD influences liver function remains obscure. Thus, we aimed to perform hepatic metabolomics in Lewis dwarf rats, a classical model of isolated GH-deficient rat, to evaluate characterizations of hepatic metabolic profiles and explore their relations with liver functions.

METHODS: Lewis dwarf homozygous (dw/dw) rats at 37 weeks (five females and five males), and Lewis dwarf heterozygous (dw/+) rats at 37 weeks (five females and five males) were analyzed in our study. The body lengths and weights, liver weights, serum ALT, and AST levels were measured. The non-targeted hepatic metabolomics was performed between dw/+ and dw/dw rats.

RESULTS: Body weights and lengths, liver weights, and serum IGF-1 levels in dw/dw rats were significantly decreased when compared with dw/+ rats. Dw/dw rats exhibited more obvious hepatic steatosis accompanied by higher serum ALT and AST levels. Hepatic metabolomics showed that a total of 88 and 51 metabolites were identified in positive and negative modes, respectively. Seven metabolites (LPC 16:2, LPC 18:3, LPC 22:6, FAHFA18:1, palmitoyl acid, dehydrocholic acid and 7-Ketolithocholic acid) were significantly altered. These seven differential metabolites were significantly associated with abnormal phenotypes. KEGG pathway analysis showed that arginine and proline metabolism and bile secretion pathways were mainly clustered.

CONCLUSION: Lewis dw/dw rats with isolated growth hormone deficiency (IGHD) showed liver steatosis and abnormal liver function, which could be potentially associated with distinctive hepatic metabolic profiles.