Vanderbilt University researchers explored the changes in immune cell populations in subjects who were obese, in those who lost weight, and in those that had recurrent fluctuation of weight—also termed "weight cycling [WC]." This work, published in Nature Communications, reveals that it is the fluctuating weight gain and loss, not just the gain itself, that can have greater adverse impacts on physical health.

Senior author, Alyssa Hasty, PhD, professor of molecular physiology and biophysics and associate dean for faculty of the basic sciences at the Vanderbilt University School of Medicine, and team (which included Matthew Cottam, recent PhD graduate, and postdoctoral fellow Heather Caslin) explored the changes in immune cell populations found in fat tissue that are present during obesity, weight loss. 

In their pursuit to understand the immunological causes of WC–accelerated metabolic disease, the researchers used what they described as a "cellular indexing of transcriptomes and epitopes by sequencing (CITEseq)" in male mice to identify the imprinting of adipose tissue (AT) immune cells that remained detectable during weight loss but progressively more so when the weight was regained. As a consequence of this weight loss and gain cycle, immunometabolic adaptations that occurred in AT resulted in an impaired recovery of type 2 regulatory cells, activation of antigen presenting cells, T-cell exhaustion, and enhanced lipid handling in macrophages in the weight-cycled mice.

Dr. Hasty, who specializes in immunometabolism (specifically the role the immune system plays in obesity and metabolic disease), provided some insight in a recent media interview where she described the goal of her research and the problem she was seeking to address. "Weight loss is hard to maintain, and many individuals regain lost weight within a few years. Unfortunately, weight cycling—the process of losing and then regaining weight—is a greater diabetes risk than obesity itself. We know that adipose immune cells contribute to obesity-related disease risk, but less is understood about the role of adipose immune cells in weight cycling," Dr. Hasty stated.

She went on to explain her research technique, using single-cell sequencing as an effort to provide high-resolution data to detect differences in individual cell function in a specific "micro-environment." She added that barcoding or tagging the samples with antibodies provided a unique chance to analyze the biological replicates.

The authors concluded that "weight loss is known to improve metabolic outcomes associated with obesity. However, low success rates and failure to maintain lost weight are common, with recent studies reporting that most individuals (>60%) regain weight within a few years." The authors highlighted that the concept of repeated cycles of weight loss and gain "further increases risk for developing diabetes and cardiometabolic diseases."

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