Neprilysin activity is increased in metabolic dysfunction-associated steatotic liver disease and normalizes after bariatric surgery or GLP-1 therapy.

Inhibitors of neprilysin improve glycemia in patients with heart failure and type 2 diabetes (T2D). The effect of weight loss by diet, surgery, or pharmacotherapy on neprilysin activity (NEPa) is unknown. We investigated circulating NEPa and neprilysin protein concentrations in obesity, T2D, metabolic dysfunction-associated steatotic liver disease (MASLD), and following bariatric surgery, or GLP-1-receptor-agonist therapy.

A Gut-Intrinsic Melanocortin Signaling Complex Augments L-Cell Secretion in Humans.

Objective: Hypothalamic melanocortin 4 receptors (MC4R) are a key regulator of energy homeostasis. Brain-penetrant MC4R agonists have failed, as concentrations required to suppress food intake also increase blood pressure. However, peripherally located MC4R may also mediate metabolic benefits of MC4R activation.

GLP-1 Receptor Agonist Treatment in Morbid Obesity and Type 2 Diabetes Due to Pathogenic Homozygous Melanocortin-4 Receptor Mutation: A Case Report.

Individuals with obesity due to pathogenic heterozygous () mutations can be treated efficiently with the glucagon-like peptide-1 receptor agonist (GLP-1 RA) liraglutide. Here, we report the effect of 16 weeks of liraglutide 3 mg/day treatment in a woman with morbid obesity and type 2 diabetes (T2D) due to homozygous pathogenic mutation. The body weight loss was 9.

Adults with pathogenic MC4R mutations have increased final height and thereby increased bone mass.

Pathogenic mutations in the melanocortin-4 receptor (MC4R) are associated with obesity, increased linear growth, and higher bone mass in children, and rodent studies have indicated an effect of the MC4R on bone turnover. Furthermore, GLP-1 receptor agonists (GLP-1 RAs) may influence bone metabolism. However, these associations have not been assessed in adults with pathogenic MC4R mutations.

Patients with Obesity Caused by Melanocortin-4 Receptor Mutations Can Be Treated with a Glucagon-like Peptide-1 Receptor Agonist.

Pathogenic mutations in the appetite-regulating melanocortin-4 receptor (MC4R) represent the most common cause of monogenic obesity with limited treatment options. Glucagon-like peptide-1 receptor agonists (GLP-1 RAs) cause weight loss by reducing appetite. We assessed the effect of the GLP-1 RA liraglutide 3.