Most people who lose weight regain it. This isn't a personal failing — it's biology. And it matters enormously, because weight cycling isn't simply a return to baseline. We have shown that these cycles of weight loss and regain actively accelerate atherosclerosis and worsen systemic inflammation beyond what is seen with stable obesity — even when final body weight is identical.
The reason, we discovered, lies in the bone marrow. Weight cycling reprograms immune progenitors — the cells that continuously produce macrophages, neutrophils, and other immune cells — toward a persistently hyperinflammatory state. The immune system, it turns out, remembers the metabolic turbulence of weight cycling long after the weight itself is gone.
We are now asking how this memory is encoded. What metabolic shifts in immune progenitors drive their inflammatory reprogramming? What epigenetic marks lock in this state and pass it to daughter cells? And critically — are these changes reversible?

GLP-1 receptor agonists like semaglutide (Ozempic/Wegovy) have transformed obesity treatment — reducing not just weight but also systemic inflammation and cardiometabolic disease risk. But most patients stop taking them, and when they do, weight returns rapidly. What happens to the immune system after cessation is one of the most pressing unanswered questions in cardiometabolic medicine.
Using our mouse models and patient samples we are now uncovering how GLP-1R activation rewires immune cell metabolism and epigenetics, and whether these changes can be sustained or induced without the drug.
We are also investigating how these drugs influence the adipose tissue, and subsequently its crosstalk between the heart vasculature and fat. This international ADAMANT network (funded by the Leducq Foundation), is a collaborate with investigators at NYU, Karolinska Institute, Aarhus University, and The Rockefeller University 
For the millions who cycle on and off these medications, understanding what the drug leaves behind in the immune system could transform how we think about — and protect — long-term cardiometabolic health.

An emerging direction in the lab asks whether the harmful effects of weight cycling extend to female reproduction. With the growing use of GLP-1 receptor agonists — and clinical guidelines recommending discontinuation before pregnancy — weight cycling prior to conception is becoming increasingly common.
Our preliminary findings show that weight cycling, compared to stable obesity, worsens placental inflammation, increases rates of fetal growth restriction, and reduces viable offspring at birth in mouse models. We are now investigating the immune mechanisms underlying these effects, with the goal of informing clinical guidelines and identifying targets to protect reproductive outcomes in women with obesity.

Obesity drives a state of chronic, low-grade inflammation that fuels cardiovascular disease, diabetes, cancer and other metabolic conditions. Weight loss is the most powerful way to reverse these complications — but how weight loss achieves this at the cellular level remains poorly understood.
Our lab discovered that caloric restriction-induced weight loss triggers the accumulation of a distinct macrophage subtype in visceral adipose tissue. These "CR-macrophages" are characterized by high expression of the phagocytic receptor Fcgr4, which drives their enhanced ability to promote metabolic health.
 
We are now defining how these macrophages arise, what sustains them, and whether they can be harnessed therapeutically — including through targeted mRNA delivery — to reverse obesity complications independent of weight loss itself. This work is supported by the NIH NIDDK (R01 DK140331).