Adiposity, immunity, and inflammation: interrelationships in health and disease: a report from 24th Annual Harvard Nutrition Obesity Symposium, June 2023.

The rapidly evolving field of immunometabolism explores how changes in local immune environments may affect key metabolic and cellular processes, including that of adipose tissue. Importantly, these changes may contribute to low-grade systemic inflammation. In turn, chronic low-grade inflammation affecting adipose tissue may exacerbate the outcome of metabolic diseases. Novel advances in our understanding of immunometabolic processes may critically lead to interventions to reduce disease severity and progression. An important example in this regard relates to obesity, which has a multifaceted effect on immunity, activating the proinflammatory pathways such as the inflammasome and disrupting cellular homeostasis. This multifaceted effect of obesity can be investigated through study of downstream conditions using cellular and systemic investigative techniques. To further explore this field, the National Institutes of Health P30 Nutrition Obesity Research Center at Harvard, in partnership with Harvard Medical School, assembled experts to present at its 24th Annual Symposium entitled "Adiposity, Immunity, and Inflammation: Interrelationships in Health and Disease" on 7 June, 2023. This manuscript seeks to synthesize and present key findings from the symposium, highlighting new research and novel disease-specific advances in the field. Better understanding the interaction between metabolism and immunity offers promising preventative and treatment therapies for obesity-related immunometabolic diseases.

Protocol for a randomized placebo-controlled clinical trial using pure palmitoleic acid to ameliorate insulin resistance and lipogenesis in overweight and obese subjects with prediabetes.

Palmitoleic acid (POA), a nonessential, monounsaturated omega-7 fatty acid (C16:1n7), is a lipid hormone secreted from adipose tissue and has beneficial effects on distant organs, such as the liver and muscle. Interestingly, POA decreases lipogenesis in toxic storage sites such as the liver and muscle, and paradoxically increases lipogenesis in safe storage sites, such as adipose tissue. Furthermore, higher POA levels in humans are correlated with better insulin sensitivity, an improved lipid profile, and a lower incidence of type-2 diabetes and cardiovascular pathologies, such as myocardial infarction. In preclinical animal models, POA improves glucose intolerance, dyslipidemia, and steatosis of the muscle and liver, while improving insulin sensitivity and secretion. This double-blind placebo-controlled clinical trial tests the hypothesis that POA increases insulin sensitivity and decreases hepatic lipogenesis in overweight and obese adult subjects with pre-diabetes. Important to note, that this is the first study ever to use pure (>90%) POA with < 0.3% palmitic acid (PA), which masks the beneficial effects of POA. The possible positive findings may offer a therapeutic and/or preventative pathway against diabetes and related immunometabolic diseases.