With the rise in the use of glucagon-like peptide-1 (GLP-1) receptor agonists, the impact of weight fluctuation and weight maintenance is an especially relevant topic for clinicians who prescribe these drugs or other interventions for weight loss. The subject will be the focus of Beyond the Scale—Exploring Causes and Consequences of Weight Fluctuation on Monday, June 24, from 8:00 a.m. – 9:30 a.m. ET in Room W307 of the Orange County Convention Center.

Iris Shai, PhD, Professor of Nutrition and Epidemiology at Ben Gurion University of the Negev, Beersheba, Israel, and Adjunct Professor at Harvard School of Public Health, will review signs of antiaging in weight loss and lifestyle interventions in the context of the landmark findings unveiled in four long-term, large-scale compressive dietary randomized controlled trials: DIRECT, CASCADE, CENTRAL, and DIRECT-PLUS.

DIRECT compared the effects of dietary strategies on cardiometabolic risk and plaque regression. DIRECT-PLUS explored the effects of a green Mediterranean diet on the gut-fat-brain axis and found that the regimen, which is rich in dietary polyphenols, led to greater reductions in visceral and ectopic fat, improved glycemic control, and enhanced biological age attenuation, Dr. Shai noted.

“If you switch and change your lifestyle, even with moderate weight loss, you could change a lot to attenuate your age-related brain atrophy and vascular aging and improve and optimize your microbiome and epigenetics,” she said. “Green dietary polyphenols might enhance this effect.”

While participants in CENTRAL, a whole-body MRI trial focused on human-specific fat deposits and fuel metabolism across dietary strategies, achieved moderate weight loss after the partial regain phase, the findings demonstrated that adopting a healthy diet and lifestyle can benefit signs of antiaging related to MRI-assessed brain and vascular aging, the microbiome, and epigenetics within 18 months to two years.

CASCADE studied the effect of moderate alcohol consumption in type 2 diabetes.

Heather Caslin, PhD, Assistant Professor, Laboratory of Integrated Physiology at the University of Houston, will address how adipose immune cells “remember” weight gain and loss and how those changes may exacerbate disease risk following weight regain. Mounting evidence suggests that while weight loss improves clinical parameters of metabolic health, weight regain can worsen the risk for cardiometabolic diseases like type 2 diabetes.

“In our mouse model of weight cycling, weight loss improves glucose tolerance, which we look at as a proxy for diabetes risk. This is similar to the beneficial effects of weight loss for humans,” she said. “But we also show that the immune cells in the adipose tissue never go back to their homeostatic state. Even after weight loss, they remain more inflammatory or dysregulated. We think this primes the cells to contribute to the worsened diabetes risk that we see once the mice regain weight.”

After weight regain, macrophages produce even more inflammatory mediators than after the initial weight gain, which likely plays a detrimental role in disease risk, Dr. Caslin noted.

“There is a lot we still don’t understand about what drives the immune memory and how different types of diet and exercise interventions impact immune and metabolic outcomes, but I hope that this talk can inspire other researchers to consider looking at weight history in their studies or to look at the adipose immune environment,” she said.

Marcus DaSilva Goncalves, MD, PhD, Associate Professor of Medicine and of Biochemistry, Weill Cornell Medical College, will discuss how weight loss affects nutrient uptake and metabolism, including the contribution of dietary sugars to obesity and intestinal health.

“We’ve been able to target pathways in the intestine in order to block nutrient absorption and show that leads to weight loss in obese mice,” Dr. DaSilva Goncalves said.

Dr. DaSilva Goncalves will also discuss how sugar metabolism can be targeted therapeutically to prevent obesity or reverse unintentional weight loss.

“Some of the treatments we’re interested in manipulate sugar metabolism in the intestine,” he said. “For example, we’re interested in using a ketohexokinase inhibitor, which blocks fructose metabolism.” 

The session will be livestreamed on the virtual meeting platform for registered meeting participants. It also will be available on-demand following the 84^th Scientific Sessions.