GLP-1 therapy boosts visceral fat metabolism, driving weight loss

By Pooja Toshniwal PahariaReviewed by Benedette Cuffari, M.Sc.Aug 26 2024

Study reveals that GLP-1 therapy increases visceral adipose tissue metabolism, significantly contributing to weight loss in individuals with obstructive sleep apnea.

Study:  GLP-1 therapy increases visceral adipose tissue metabolic activity: lessons from a randomized controlled trial in obstructive sleep apnea. Image Credit: Lee Charlie / Shutterstock.com

In a recent study published in the journal Obesity, researchers discuss the role of enhanced visceral adipose tissue (VAT) metabolism in mediating weight loss by glucagon-like peptide-1 (GLP-1) drugs.

What is VAT metabolism?

The human body resists weight reduction due to complex homeostatic mechanisms. Conventional weight control methods often emphasize the importance of reducing caloric intake through dietary adjustments; however, this strategy has been associated with limited success.

Metabolic dysfunction in VAT is characteristic of obesity. Intermittent hypoxia in obstructive sleep apnea (OSA) involves structural and functional alterations that are similar to those observed in obesity.

GLP-1 analogs are common weight-loss medications that reduce energy intake by delaying stomach emptying and increasing satiety. In vivo experiments in mice have indicated that GLP-1 analogs affect energy balance by increasing VAT metabolism, thermogenesis, and energy expenditures; however, it remains unclear how these medications affect VAT metabolism in humans.

About the study

The current randomized control trial (RCT) evaluated the impact of GLP-1-mediated weight reduction on metabolism and early biomarkers of cardiovascular disease risk in OSA. Thirty obese and non-diabetic individuals with moderate or severe OSA with apnea/hypopnea index (AHI) values exceeding 15 occurrences every hour were included in the study. The study participants' body mass index (BMI) values were between 30 and 40 kg/m².

Over the 24-week study period, participants received the GLP-1 agonist liraglutide with gradual increments to three mg/day, continuous positive airway pressure (CPAP), or both. At the beginning and end of the trial, 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography-computed tomography (PET-CT) imaging assessed VAT metabolic activity using VAT target-to-background ratio (TBR) values.

Two radiology specialists examined the PET images, during which these physicians delineated three circular zones of interest on peripheral adipose tissues and VAT depots at the L3-L4 levels. Maximal standardized uptake (SUVmax) values were obtained by averaging these measurements. TBR values were calculated for every subject by dividing SUVmax for adipose tissue by blood pool activities in the mediastinum, which reflected the mean of three SUVmax measurements at the level of the superior vena cava (SVC).

One-way analysis of variance (ANOVA) with χ2 test or Bonferroni post hoc analysis facilitated inter-group comparisons, whereas paired parametric t-tests analyzed intra-group differences. Pearson correlations were determined, and analysis of covariance (ANCOVA) models evaluated associations between PET findings and changes in weight.

Study findings

The mean age of the study participants was 50, 80% of whom were male. Most suffered from severe OSA, with mean AHI values of 50 events/hour. The average values for adherence to CPAP among the CPAP-only and combined groups were 5.80 and 4.70 hours each night, respectively.

Self-reports of liraglutide adherence were similarly high. CPAP, individually or combined, successfully treated OSA with AHI values of three and five occurrences/hour, respectively.

Liraglutide also improved AHI values to 42 events/hour, although to a lower extent than the other groups. Liraglutide treatment, both alone and in combination with CPAP, led to a significant weight reduction of 6.2 and 3.7 kgs, respectively, which was not observed with CPAP alone.

Using PET-CT to examine metabolism in VAT depots, no difference in TBR values was observed for peripheral adipose tissues with any experimental strategy. Comparatively, GLP-1 treatment significantly increased VAT metabolism. The combination therapy also resulted in a slight but statistically non-significant increase in visceral adipose tissue TBR values, whereas CPAP did not affect VAT TBR.

Significant correlations were observed between the extent of high VAT target-to-background ratio values and weight reduction. Lower baseline VAT metabolism levels were associated with greater weight reduction by GLP-1 medications, thus indicating that people with low VAT metabolic activities might benefit the most from the dual effects of GLP-1 treatment on reduced calorie intake and enhanced metabolic activity.

Conclusions

The study findings confirm that GLP-1 augments VAT metabolism, thereby contributing to its weight reduction effect in individuals. Moreover, poor VAT metabolism at baseline could predict a positive response to GLP-1 treatment for weight reduction.

Future studies are needed to compare this treatment approach to other weight loss methods to further elucidate the role of GLP-1 agonists in weight loss. Further research into how GLP-1 receptors control VAT metabolism would also provide important insights into the influence of gut hormone-based therapies on weight changes.