(P27-007-23) A High-Fat Diet Exacerbates Liver Steatosis but Not Hepatic Inflammation in a Clinically Relevant Rodent Model of Spinal Cord Injury-Induced Non-Alcoholic Steatohepatitis

Objectives: Neurogenic non-alcoholic steatohepatitis (nNASH) is rapidly induced following spinal cord injury (SCI) independent of obesity. Yet, 62% of individuals after SCI develop obesity-related complications and 27% of injured persons are obese prior to SCI. Because obesity and SCI likely interact to impact nNASH-associated pathology, we hypothesized that a high-fat diet (HFD) prior to SCI would exacerbate hepatic inflammation and lipogenesis.

Methods: Male Sprague Dawley rats (n = 24; 3-mo old) were provided a low-fat diet (LFD; 10% energy from fat) or a HFD (45% fat) for 3-wk. Equal numbers from each dietary treatment then received a laminectomy or thoracic contusion injury (200 kD). Hindlimb locomotor recovery was assessed using the Basso, Beattie and Bresnahan locomotor rating scale before sacrificing rodents at 28 days post-injury. Liver steatosis was assessed histologically, hepatic lipogenic gene expression by qPCR, and hepatic CLEC4F (a biomarker of Kupffer cells) by immunohistochemistry. Data were analyzed by 2-way ANOVA to examine the effects of HFD, SCI, and their interaction.

Results: At study termination, body mass was independently increased by HFD and SCI with no significant HFDxSCI interaction, whereas only SCI impaired locomotor recovery. HFD rats subjected to SCI had increased serum triglyceride compared with all other groups. Serum glucose was unaffected regardless of HFD or SCI. Although hepatic lipid accumulation was unaffected by SCI in LFD rats, it was increased among HFD rats, and potentiated by SCI in HFD rats. Neither Srebp1c nor Dgat1 mRNA expression was affected by SCI or HFD, and SCI only increased mRNA expression of Fasn and Scd1 in LFD rats. However, positive immunohistochemical staining towards CLEC4F was increased by HFD and SCI but without any statistically significant interaction.

Conclusions: Hepatic steatosis but not Kupffer cell accumulation was exacerbated by a HFD in SCI-induced nNASH. This pathology occurred without altering hepatic lipogenesis, suggesting that other lipid metabolism pathways likely potentiate HFD/SCI-induced nNASH.

Funding Sources: This work was supported by the NIH NIDDK.