Assessing the Ability to Reverse High Fat High Sugar Diet-Induced Hepatic Steatosis by Dietary Modification

Background: Metabolic syndrome includes a plethora of symptoms ultimately leading to obesity and type 2 diabetes. Increased consumption of ‘Western diets’ rich in fat and sugar increase the development of metabolic syndrome, diabetic obesity and furthermore increase the risk of non-alcoholic fatty liver disease. We aimed to better understand the influence of chronic consumption of a ‘western-type’ high fat-high sugar diet (HFS) on hepatic health and moreover we assessed the ability of dietary modifications (i.e., removal of fat and sugar from the diet) to reverse these detrimental hepatic effects. This would represent what is seen clinically, advocated by a provider in a clinical setting as a first line treatment for diabetic obese patients. Methods: Thirty male C57BL/6J mice were randomly assigned into the following groups: 12-weeks HFS then 12-weeks of standard diet and water (Std), control groups were fed standard chow and water for the entire 24-weeks (lean control) or fed HFS diet for the entire 24-weeks (HFS). At the end of the 24-week diet study, livers were removed and fixed (for sectioning and staining with Oil-Red-O or trichrome and quantified with Image J) or frozen and kept at -80°C (for PCR studies and assays). Serum was collected for assays. Results: At the end of the diet study, body weight was significantly increased 1.5-fold by HFS and reduced 34% (p<0.05) in the Std group. Liver weight/body weight ratio followed the same trend as body weight. Percent fat area, total number of lipid droplets and average total lipid area were all significantly increased in the HFS group versus lean controls and were all significantly reduced by Std (p<0.05). Serum ALT activity was increased 3-fold by HFS and then reduced to lean levels by Std. Serum TNF-α and MCP1 levels followed the same trend. Serum TBARS were significantly increased 1.6-fold, but unchanged with Std. Trichrome analysis demonstrated deposition of collagen in liver from HFS fed mice (15.53% area), which was significantly reversed by the switch to Std (4.58% area). This data will be complemented with mRNA levels currently being run for collagens 1, 3, 4. Preliminary findings indicate that HFS fed mice have a significant increase in expression of collagen-1 but not collagen-3. We aim to further explore the metabolic mechanisms involved in the reversal of hepatic steatosis and fibrosis between the three diet groups. Conclusions: We conclude that removal of the HFS diet and switching to standard chow and water (Std) is an effective treatment regimen and results in robust reversal of hepatic steatosis along with reversal of collagen deposition, with concomitant beneficial changes in key serum markers of hepatic health, systemic inflammatory profile, and body/liver weight. The mechanistic pathways triggering these effects are being explored. Midwestern-Arizona Alzheimer’s consortium and Midwestern University Intramural Grant. This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.