High‐dose administration of purified cyanidin‐3‐glucose or a blackberry extract causes improved mitochondrial function but reduced content in 3T3‐L1 adipocytes

Berry consumption shows antiobesity and antidiabetic effects in animals and humans. Anthocyanin or berry extracts increase insulin sensitivity, reduce lipid droplet formation, and cause a white-to-brite phenotypic switch of adipocytes in vitro. The objective of this study was to investigate effects of cyanidin-3-glucoside (C3G) or blackberry extract (BBE) on cellular respiration of a fatty acid substrate in differentiated adipocytes. In separate experiments, 3T3-L1 adipocytes were treated with 0, 150 nM, or 50 mu M purified C3G -or- 0, 150 nM, 25 mu M, or 50 mu M C3G-equivalents from a BBE. Baseline, state-4, state-3, and uncoupled respiration states were created experimentally and measured by high-resolution respirometry. Respiration rate within each state was corrected for mitochondrial content determined by PCR. Mitochondrial content was significantly reduced with high-dose C3G and the two high-dose BBE. The high-dose C3G caused a significant increase in respiration rate for baseline, state-4, state-3, and uncoupled states compared to control and physiologic dose C3G. The intermediate-high dose (25 mu M) BBE also significantly increased respiration rate for the same states compared to control and other treatment levels of BBE; this effect was not observed at the high-dose (50 mu M) BBE. Administration of high-dose purified C3G or BBE decreased mitochondrial content but enhanced cellular respiration on a fatty acid substrate in differentiated 3T3-L1 adipocytes across several mitochondrial states. We did not observe a phenotypic switch to brite adipocytes like others, but our empirical findings in cellular respiration on a fatty acid substrate support the antiobesity effects associated with anthocyanins and berries.