Abstract:
Natural products are the cornerstone of modern therapeutics. Bilobalide was found to be effective against
hypoxia induced alterations in innate antioxidant status in our earlier study. Adipose tissue hypoxia in obesity
contributes to insulin resistance via mitochondrial dysfunctions. Mitochondria are a central control point of
many metabolic pathways and various pathophysiological conditions. In the present investigation, we
evaluated the effect of hypoxia on crucial mitochondrial functions in 3T3-L1 adipocytes and possible
protection with bilobalide. Hypoxia for 24 hours substantially increased (P # 0.05) HIF-1a expression
(5.3 fold) as well as PDK-1 expression (2.3 fold) at the protein level in 3T3-L1 adipocytes. The aconitase
enzyme activity was significantly (P # 0.05) reduced (4.5 fold) in the hypoxic group indicating an
elevated level of mitochondria-generated ROS production. It also affected mitochondrial bioenergetics
like oxygen consumption (2.23 fold), ATP synthesis (4.32 fold), and the activities of respiratory chain
complexes such as complexes I, III and IV (2.05, 2.35 & 2.9 fold) in hypoxic adipocytes. Hypoxia also
impaired (P # 0.05) mitochondrial dynamics such as mitochondrial biogenesis and fusion/fission balance
in 3T3-L1 adipocytes. Bilobalide protected the 3T3-L1 adipocytes from adverse effects of hypoxia by
safeguarding mitochondrial bioenergetics and dynamics, via downregulating HIF-1a expression. These
findings suggest that bilobalide could be used as a therapeutic agent for adipocyte hypoxia-mediated
mitochondrial dysfunctions in obesity.
