Weight-loss maintenance is accompanied by interconnected alterations in circulating FGF21-adiponectin-leptin and...

Area of Science:

• Metabolic research
• Endocrinology
• Lipidomics

Background:

• Weight loss is frequently followed by weight regain, highlighting challenges in long-term weight management.
• Understanding the endocrine and metabolic changes during weight cycling is crucial for developing effective maintenance strategies.

Purpose of the Study:

• To characterize alterations in energy-balance-regulating metabokines and sphingolipids during weight loss and maintenance.
• To investigate the impact of diet, exercise, and GLP-1 analog therapy on these molecular profiles.
• To identify distinct metabolic signatures associated with successful weight maintenance versus regain.

Main Methods:

• Profiling of metabokines and sphingolipids in adults with obesity during a low-calorie diet-induced weight loss and subsequent maintenance phases.
• Intervention groups included exercise, glucagon-like peptide-1 (GLP-1) analog therapy, combined therapy, or placebo.
• Analysis of circulating levels of GDF15, FGF21, adiponectin, leptin, ceramides, and sphingosine-1-phosphate.

Main Results:

• Growth differentiation factor 15 (GDF15) and ceramides increased transiently after initial weight loss.
• Fibroblast growth factor 21 (FGF21) was downregulated with combined exercise and GLP-1 analog therapy during maintenance.
• Weight maintenance was associated with increased adiponectin, decreased leptin, and reduced ceramide/sphingosine-1-phosphate levels, differing from regainers.

Conclusions:

• Distinct FGF21, GDF15, and ceramide responses characterize different phases of weight change.
• Weight-loss maintenance involves significant remodeling of the metabokine-sphingolipid axis.
• Metabokine-sphingolipid profiles correlate with cardiometabolic health outcomes, offering potential therapeutic targets.