GLP-1 enhances β-cell response to protein ingestion and bariatric surgery amplifies it.

Objective: The glycemic-independent actions of glucagon-like peptide-1 (GLP-1) in the prandial state in humans are unknown. We examined the contribution of GLP-1 to β-cell secretory response (primary endpoint) and glucose metabolism during protein ingestion under basal glycemia, as well as whether these responses are affected by rerouted gut after gastric bypass (GB) or sleeve gastrectomy (SG).

Methods: Insulin secretion rate (ISR) and glucose fluxes during a 50-g oral protein load were compared among 10 nondiabetic individuals with GB, 9 with SG, and 7 non-operated controls (CN), with and without intravenous infusion of exendin(9-39) (Ex-9), a GLP-1 receptor (GLP-1R) antagonist.

Dodecanedioic acid prevents and reverses metabolic-associated liver disease and obesity and ameliorates liver fibrosis in a rodent model of diet-induced obesity.

Dodecanedioic acid (DC12) is a dicarboxylic acid present in protective polymers of fruit and leaves. We explored the effects of DC12 on metabolic dysfunction-associated steatohepatitis (MASH) and obesity. DC12 supplementation (100 mg/kg/day) was added to a high-fat diet (HFD) for 8 weeks in rodents to assess its impact on obesity and MASH prevention.

Lipid metabolism in MASLD and MASH: From mechanism to the clinic.

Metabolic dysfunction-associated steatotic liver disease/steatohepatitis (MASLD/MASH) is recognised as a metabolic disease characterised by excess intrahepatic lipid accumulation due to lipid overflow and synthesis, alongside impaired oxidation and/or export of these lipids. But where do these lipids come from? The main pathways related to hepatic lipid accumulation are lipogenesis and excess fatty acid transport to the liver (due to increased lipolysis, adipose tissue insulin resistance, as well as excess dietary fatty acid intake, in particular of saturated fatty acids). Not only triglycerides but also other lipids are secreted by the liver and are associated with a worse histological profile in MASH, as shown by lipidomics.

Hepatic glucose production rises with the histological severity of metabolic dysfunction-associated steatohepatitis.

Metabolic dysfunction-associated steatotic liver disease (MASLD) and steatohepatitis (MASH) are associated with a high prevalence of type 2 diabetes (T2D). Individuals with MASLD exhibit insulin resistance (IR) and hyperglycemia, but it is unclear whether hepatic glucose production (HGP) is increased with MASLD severity. We evaluated HGP in a cohort of histologically characterized individuals with MASL/MASH using stable isotope infusion (6,6-H-glucose, U-H-glycerol) and liver-specific genome-scale metabolic models (GEMs).