{Reference Type}: Journal Article
{Title}: Histological improvements following energy restriction and exercise: The role of insulin resistance in resolution of MASH.
{Author}: Mucinski JM;Salvador AF;Moore MP;Fordham TM;Anderson JM;Shryack G;Cunningham R;Lastra G;Gaballah AH;Diaz-Arias A;Ibdah JA;Rector RS;Parks EJ;
{Journal}: J Hepatol
{Volume}: 0
{Issue}: 0
{Year}: 2024 Jun 22
{Factor}: 30.083
{DOI}: 10.1016/j.jhep.2024.06.017
{Abstract}: <B>OBJECTIVE: </B>Metabolic-dysfunction associated steatohepatitis (MASH) is one of the most common liver diseases worldwide and is characterized by multi-tissue insulin resistance. The effects of a 10-month energy restriction and exercise intervention on liver histology, anthropometrics, plasma biochemistries, and insulin sensitivity were compared to standard of care (control) to understand mechanisms that support liver health improvements.<BR><B>METHODS: </B>Following medical diagnosis of MASH, subjects were randomized to treatment (n=16) or control (n=8). Liver fat (MRS), 18-hour plasma biochemical measurements, and isotopically-labeled hyperinsulinemic-euglycemic clamps were completed pre- and post-intervention. Body composition and cardiorespiratory fitness (VO2peak) were also measured mid-intervention. Treatment subjects were counseled to reduce energy intake and completed supervised, high-intensity interval training (3x/week) for 10 months. Control subjects continued physician-directed care.<BR><B>RESULTS: </B>Treatment induced significant (P<0.05) reductions in body weight, fat mass, and liver injury, while VO2peak (P<0.05) and fatty acid (NEFA) suppression (P=0.06) were improved. Both groups exhibited reductions in total energy intake, HbA1c, hepatic insulin resistance, and liver fat (P<0.05). Compared to control, treatment induced a two-fold increase in peripheral insulin sensitivity which was significantly related to higher VO2peak and resolution of liver disease, despite no group differences in peripheral insulin sensitivity.<BR><B>CONCLUSIONS: </B>Exercise and energy-restriction elicited significant and clinically-meaningful treatment effects on liver health, potentially driven by a redistribution of excess nutrients to skeletal muscle, thereby reducing hepatic nutrient toxicity. Clinical guidelines should emphasize the addition of aerobic exercise in lifestyle treatments for the greatest histologic benefit in individuals with advanced MASH.<BR><B>BACKGROUND: </B>NCT03151798.