Hormonal
Systemic inhibition of the chromatin modifier LSD1 using GSK-LSD1 or SP2509 reduces body weight, improves insulin sensitivity, and reverses nonalcoholic fatty liver disease (NAFLD) in obese mouse models, independent of reduced food intake.
Targeting the enzyme LSD1 appears to fix the underlying metabolic dysfunction in obesity, not just cause weight loss. It reduces fat tissue inflammation and stops fat from flooding the liver, improving insulin sensitivity directly. This suggests that future drugs targeting LSD1 could treat obesity and its complications like fatty liver and diabetes simultaneously, rather than just suppressing appetite.
We show that systemic administration of an LSD1 inhibitor (GSK-LSD1) reduces food intake and body weight, ameliorates nonalcoholic fatty liver disease (NAFLD), and improves insulin sensitivity and glycemic control in mouse models of obesity... Pair-feeding experiments further revealed that effects of GSK-LSD1 on hyperglycemia and NAFLD are not a consequence of reduced food intake and weight loss.
Why this rating
High-quality pharmacological intervention in well-established genetic and diet-induced obesity models with rigorous controls (pair-feeding, lean controls).
Source
Systemic LSD1 Inhibition Prevents Aberrant Remodeling of Metabolism in Obesity
Bastian Ramms et al. · Diabetes · 2022
DOI 10.2337/db21-1131
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