Scd1 controls de novo beige fat biogenesis through succinate-dependent regulation of mitochondrial complex II

Abstract

Preadipocytes can give rise to either white adipocytes or beige adipocytes. Owing to their distinct abilities in nutrient storage and energy expenditure, strategies that specifically promote “beiging” of adipocytes hold great promise for counterbalancing obesity and metabolic diseases. Yet, factors dictating the differentiation fate of adipocyte progenitors remain to be elucidated. We found that stearoyl-coenzyme A desaturase 1 (Scd1)-deficient mice, which resist metabolic stress, possess augmentation in beige adipocytes under basal conditions. Deletion of Scd1 in mature adipocytes expressing Fabp4 or Ucp1 did not affect thermogenesis in mice. Rather, Scd1 deficiency shifted the differentiation fate of preadipocytes from white adipogenesis to beige adipogenesis. Such effects are dependent on succinate accumulation in adipocyte progenitors, which fuels mitochondrial complex II activity. Suppression of mitochondrial complex II by Atpenin A5 or oxaloacetic acid reverted the differentiation potential of Scd1-deficient preadipocytes to white adipocytes. Furthermore, supplementation of succinate was found to increase beige adipocyte differentiation both in vitro and in vivo. Our data reveal an unappreciated role of Scd1 in determining the cell fate of adipocyte progenitors through succinate-dependent regulation of mitochondrial complex II.

Pleiotropic role of melatonin in brain mitochondria of obese mice

“…The recovery of the complexes III, IV and complex I leads to a reduction in the expression levels of the complex II to its control level under its exacerbated expression caused by obesity. This was also observed under fat biogenesis (68). This reduction in the complex II implies a consequent reduction in the activity of the complex II and, with it, an elevated intracellular SUC (69).…”

“…The differentiation of these cells was predominantly directed to the beige adipocyte, rather than to white adipocyte under suppression of mitochondrial complex II. This study showed a prominent role of UCPs in this process (68). Herein, a significant increase in UCP2 expression was induced by melatonin in obese animals, being coordinated and combined with a measured complex V reduction and a decline in ATP synthesis.…”

Stearoyl-CoA Desaturase Is Essential for Porcine Adipocyte Differentiation

“…It has been reported that the global disruption of SCD1 in mice reduces body adiposity and increases insulin sensitivity, making mice resistant to diet-induced weight gain [8]. Recently obtained data revealed the unappreciated role of SCD1 in potentiating beige adipocyte formation in mice [25]. These observations suggest that SCD is a promising candidate gene for reducing fat deposition in pigs, and the mechanisms that precisely regulate the SCD activity in adipose tissues need to be further explored.…”

Mitochondrial donation in translational medicine; from imagination to reality

“…This process includes food conversion to energy in response to the energy demands by synthesizing blocks for proteins, lipids, nucleic acids, and carbohydrates; and the elimination of nitrogenous wastes. With the promotion of cell metabolism, various intermediate factors are interchanged between the cells in a tightly regulated manner [ 8 ]. Both catabolic and anabolic metabolic reactions are tightly regulated under physiological conditions.…”