Convertible visceral fat as a therapeutic target to curb obesity

Abstract

New therapeutic and preventative strategies are needed to address the growing obesity epidemic. In animal models, brown adipose tissue activation and the associated heat produced contribute to countering obesity and the accompanying metabolic abnormalities. Adult humans also have functional brown fat. Here, we present and discuss the concepts of murine and human white adipose tissue plasticity and the transdifferentiation of white adipocytes into brown adipocytes. Human visceral adipocytes - which are crucial contributors to the burden of obesity and its complications - are particularly susceptible to such transdifferentiation. Therefore, we propose that this process should be a focus of anti-obesity research. Approved drugs that have browning properties as well as future drugs that target molecular pathways involved in white-to-brown visceral adipocyte transdifferentiation may provide new avenues for obesity therapy.

Blocking FSH induces thermogenic adipose tissue and reduces body fat

“…The use of anti-obesity agents, consisting mainly of those that reduce appetite or inhibit nutrient absorption, is compromised by issues of poor efficacy and unacceptable side effects 34 . Thus, the therapeutic armamentarium for obesity currently pales in comparison with that of other public health hazards of similar or lesser magnitudes, such as hypertension, diabetes or osteoporosis.…”

Macrophage functions in lean and obese adipose tissue

“…However, cannabinoid receptor type 2 receptor polymorphisms are associated with obesity and the cannabinoid receptor type 2 agonist JWH-133 enhanced adipocyte UCP-1 expression (consistent with a browning effect) and hindered IL-6 release 56 . In addition to these potential candidates for drug development, several other classes of molecules are in clinical trials for obesity modulate brown fat and energy intake and expenditure and have been reviewed 57 .…”

Heterogeneity of adipose tissue in development and metabolic function

“…1). BAT activity can be increased upon cold exposure and noradrenergic stimulation, and also pharmacologically (Giordano et al, 2016) and by fasting (Migliorini et al, 1997). In humans, active BAT was believed to be only present in the neck and shoulder of newborns and small children, where its function was attributed to be maintenance of body temperature upon cold exposure to compensate for the lack of shivering-thermogenesis (Lean, 1989).…”