Piceatannol induces regulatory T cells and modulates the inflammatory response and adipogenesis.

The beneficial effects of the polyphenolic compound piceatannol (PC) has been reported for metabolic diseases, antiproliferative, antioxidant, and anti-cancer properties. Despite its beneficial effects on inflammatory diseases, little is known about how PC regulates inflammatory responses and adipogenesis. Therefore, this study was designed to determine the effects of PC on the inflammatory response and adipogenesis. The effect of PC on splenocytes, 3T3-L1 adipocytes, and RAW264.7 macrophages was analyzed by flow cytometry, qRT-PCR, morphometry, and western blot analysis. PC induced apoptosis in activated T cells in a dose-dependent manner using stimulated splenocytes and reduced the activation of T cells, altered T cell frequency, and interestingly induced the frequency of regulatory T (Treg) cells as compared to controls. PC suppressed the expression of TNF-α, iNOS, IL-6R, and NF-κB activation in RAW264.7 macrophages after lipopolysaccharides (LPS)-induction as compared to the control. Interestingly, PC altered the cell morphology of 3T3-L1 adipocytes with a concomitant decrease in cell volume, lipid deposition, and TNF-α expression, but upregulation of leptin and IL-1ß. Our findings suggested that PC induced apoptosis in activated T cells, decreased immune cell activation and inflammatory response, and hindered adipogenesis. This new set of data provides promising hope as a new therapeutic to treat both inflammatory disease and obesity.

Exogenous mitochondrial transfer increases energy expenditure and attenuates adiposity gains in mice with diet-induced obesity.

Obesity is associated with chronic multi-system bioenergetic stress that may be improved by increasing the number of healthy mitochondria available across organ systems. However, treatments capable of increasing mitochondrial content are generally limited to endurance exercise training paradigms, which are not always sustainable long-term, let alone feasible for many patients with obesity. Recent studies have shown that local transfer of exogenous mitochondria from healthy donor tissues can improve bioenergetic outcomes and alleviate the effects of tissue injury in recipients with organ specific disease. Thus, the aim of this project was to determine the feasibility of systemic mitochondrial transfer for improving energy balance regulation in the setting of diet-induced obesity. We found that transplantation of mitochondria from lean mice into mice with diet-induced obesity attenuated adiposity gains by increasing energy expenditure and promoting the mobilization and oxidation of lipids. Additionally, mice that received exogenous mitochondria demonstrated improved glucose uptake, greater insulin responsiveness, and complete reversal of hepatic steatosis. These changes were, in part, driven by adaptations occurring in white adipose tissue. Together, these findings are proof-of-principle that mitochondrial transplantation is an effective therapeutic strategy for limiting the deleterious metabolic effects of diet-induced obesity in mice.