Cooling down with Entresto. Can sacubitril/valsartan combination enhance browning more than coldness?

Abstract

Background It is a growing importance to induce a new treatment approach to encourage weight loss but also to improve maintenance of lost weight. It has been shown that promotion of brown adipose tissue (BAT) function or acquisition of BAT characteristics in white adipose tissue (terms referred as “browning”) can be protective against obesity. Main text Amongst numerous established environmental influences on BAT activity, cold exposure is the best interested technique due to its not only effects on of BAT depots in proliferation process but also de novo differentiation of precursor cells via β-adrenergic receptor activation. A novel combination drug, sacubitril/valsartan, has been shown to be more efficient in reducing cardiovascular events and heart failure readmission compared to conventional therapy. Also, this combination of drugs increases the postprandial lipid oxidation contributing to energy expenditure, promotes lipolysis in adipocytes and reduces body weight. To date, there is no research examining potential of combined sacubitril/valsartan use to promote browning or mechanisms in the basis of this thermogenic process. Conclusion Due to the pronounced effects of cold and sacubitril/valsartan treatment on function and metabolism of BAT, the primary goal of further research should focused on investigation of the synergistic effects of the sacubitril/valsartan treatment at low temperature environmental conditions.

Sacubitril/valsartan promotes white adipose tissue browning in rats with metabolic syndrome through activation of mTORC1

“…However, finding pharmacological manipulation that will favor brown-like adipocytes in WAT depots influencing overall glucose metabolism and energy homeostasis still represents the primarily focus of many investigations. 5 In order to examine the mechanism by which 4-week Sac/Val treatment induces browning in rats with MetS, we investigated the influence of Sac/Val administration on the morphological changes in different adipose tissue depots (sWAT, rWAT, and eWAT). Histological analysis confirmed that MetS induction resulted in increased cell size in each examined adipose tissue related with the accumulation of lipid droplets.…”

“…Val, as an antagonist of AT1 receptors, partially activates PPARγ which acts as the master regulators of adipogenesis. 5 Recent evidence implied strong correlation between PPARγ stimulation and mTORC1 activation in the management of fat cell metabolism. While PPARγ-mTORC1 activation leads to increased adiponectin production and its secretion in WAT, the downregulation of mTORC1 decreased adipose tissue activity of PPARγ as one of the main regulators of adipogenesis.…”

“…Even though white adipocytes are primary sites for lipid storage in the form of triglycerides, WAT depots differ in their secretory and metabolic functions. 5 In contrast, BAT utilizes the energy of the stored lipid droplets and releases it in the form of heat in the process named as "nonshivering thermogenesis." This phenomenon occurs primarily due to the action of uncoupling protein-1 (UCP-1), a transmembrane protein which facilitates heat production by uncoupling adenosine triphosphate (ATP) synthesis.…”

“…This phenomenon occurs primarily due to the action of uncoupling protein-1 (UCP-1), a transmembrane protein which facilitates heat production by uncoupling adenosine triphosphate (ATP) synthesis. 5,6 Apart from the usual interscapular localization of BAT, brownlike cells named as beige adipocytes appear in some WAT depots in response to various stimuli (so called "browning"). 7 Considering that beige adipocytes also enhance heat generation as BAT, recent evidence suggests that promoting beige cells in WAT depots is a promising therapeutic strategy to fight with obesity and its related metabolic diseases.…”