Manassantin B attenuates obesity by inhibiting adipogenesis and lipogenesis in an AMPK dependent manner.

ABSTRACT

Saururus chinensis (S chinensis) has been used as an herb to treat edema, jaundice, and gonorrhea. Manassantin B (MNSB), a dineolignan isolated from S chinensis, was identified as a potent adipogenesis/lipogenesis inhibitor (IC50  = 9.3 nM). To explore the underlying mechanism, both adipogenesis and lipogenesis were measured in differentiated 3T3-L1 preadipocytes, murine primary preadipocytes and adipose tissue explants upon MNSB treatment. Key regulators of adipogenesis/lipogenesis were downregulated by MNSB treatment, mainly resulting from increased phosphorylation of AMPK which was identified as a vital regulator of adipogenesis and lipogenesis. Moreover, MNSB did not increase AMPK phosphorylation in 3T3-L1 cells transfected with Prkaa1 (encoding protein kinase AMP-activated catalytic subunit alpha 1) siRNA or adipose tissue explants isolated from adipose-specific Prkaa1-disrupted mice (Prkaa1Δad ). In diet-induced obese C57BL/6N mice, MNSB displayed preventive and therapeutic effects on obesity accompanied by decreased adipocyte size. MNSB was also found to increase AMPK phosphorylation both in subcutaneous white adipose tissue and brown adipose tissue in vivo. These findings suggest that MNSB can be a new therapeutic agent for the prevention and treatment of obesity and other related metabolic disorders.