Background: Increased adiposity has long been associated with insulin resistance and adipose tissue plays a crucial role in regulating metabolic homeostasis, as its dysfunction in obesity leads to insulin resistance and type 2 diabetes (T2D). The primary function of white adipose tissue (WAT) is to store energy as lipids while brown adipose tissue (BAT) regulates thermogenesis by dissipating energy in a form of heat. The process of browning involves transdifferention of WAT into brown-like or beige adipocytes, which exhibit the same functional properties as BAT. Browning of WAT is an attractive approach against obesity and insulin resistance. In addition, evidence indicate that activation of the energy sensor AMP-activated protein kinase (AMPK) could counteract insulin resistance. The aim of this study is to examine if carnosic acid (CA), induces browning via activation of AMPK in 3T3-L1 white adipocytes.

Material and methods: Cell morphology, lipid accumulation, mitochondrial density, and browning markers such as uncoupling protein-1 (UCP-1) and peroxisome proliferator-activated receptor gamma coactivator-1 alpha (PGC-1α) levels were assessed using Cytation5 microscope, Oil-O-Red (ORO), MitoTracker Red, immunoblotting and immunocytochemistry.

Results: Microscopic investigation revealed that CA reduced the size and number of lipid droplets in the cells, giving a rise to a brown-like phenotype. The reduction of lipid accumulation was also confirmed by ORO stain. Next, CA increased mitochondrial density and protein expression of UCP-1 and PGC-1-α in 3T3-L1 adipocytes. Most importantly, pre-treatment with compound C, prevented the CA-induced reduction in lipid accumulation, and mitochondrial density and blocked the CA-induced increase in UCP-1 and PGC-1 expression.

Conclusion: This study demonstrates that CA has a pronounced potential in stimulating browning of adipocytes via AMPK-dependent mechanism. Future in vivo studies are required to fully examine the effects of CA.


F.Vlavcheski: None. N.Tsakiridis: None. A.Giacca: None. E.Tsiani: None.


Natural Science and Engineering Research Council of Canada (RGPIN-2018-06666)

Readers may use this article as long as the work is properly cited, the use is educational and not for profit, and the work is not altered. More information is available at