Fatty Acylcarnitine Metabolism in Brown/Beige and White Fats by ¹³C HRMAS NMR Spectroscopy With Metabolic...

White adipose tissue (WAT) and brown adipose tissue (BAT) have distinct structural and physiological characteristics and serve opposing functions in the body. WAT primarily stores energy, whereas BAT is metabolically active and positively influences metabolic health, contributing to energy expenditure, reduced fat accumulation and enhanced mitochondrial metabolism. Recently, both classical BAT and beige fat (or inducible/recruitable BAT) that arises from the browning of WAT have attracted clinical interest as potential targets for improving mitochondrial metabolism and managing obesity-related metabolic disorders. Currently, there is a lack of specific metabolic biomarkers for characterizing classical BAT and beige fat tissues, which are essential for evaluating mitochondrial oxidative metabolism and screening browning agents for therapeutic use. In this study, we investigated the potential metabolic biomarker fatty acylcarnitine in interscapular BAT (iBAT) from the interscapular region and beige adipose tissue from the inguinal region of the animal using ex vivo ¹³C high-resolution magic angle spinning (HRMAS) NMR spectroscopy. We examined how mitochondrial oxidative metabolism was altered in response to a high-fat diet (HFD) and how it was restored through iBAT activation using stimuli such as cold exposure and β3-adrenergic receptor (β3-AR) agonist, CL-316,243 treatment. We identified fatty acylcarnitine as a potential metabolic marker present in iBAT and beige tissues, whereas it was absent in iWAT. The concentration of fatty acylcarnitine significantly decreased in HFD-fed animals due to impaired lipolysis resulting in inefficient shuttling of fatty acids for mitochondrial β oxidation. However, its concentration increased or was restored in response to iBAT activation through either β3-AR agonist treatment or cold exposure, indicating a high-energy metabolic state with enhanced mitochondrial metabolism in iBAT. Fatty acylcarnitine shows promise as a biomarker for evaluating mitochondrial metabolism and for screening potential browning agents and nutraceuticals capable of inducing the browning of WAT.