期刊
PHARMACEUTICS
卷 14, 期 7, 页码 -出版社
MDPI
DOI: 10.3390/pharmaceutics14071368
关键词
nitric oxide; l-arginine; browning; obesity
资金
- Science Fund of the Republic of Serbia, PROMIS [6066747]
- Ministry of Education, Science and Technological Development of the Republic of Serbia [451-03-68/2022-14/200007]
L-arginine supplementation induces browning of white adipose tissue, characterized by the appearance of multilocular adipocytes and increased expression of thermogenic and beige adipocyte-specific genes. This browning effect is associated with increased inducible nitric oxide protein expression and NO signaling. Additionally, L-arginine treatment also decreases white adipose tissue mass and body weight.
The beneficial effects of l-arginine supplementation in obesity and type II diabetes involve white adipose tissue (WAT) reduction and increased substrate oxidation. We aimed to test the potential of l-arginine to induce WAT browning. Therefore, the molecular basis of browning was investigated in retroperitoneal WAT (rpWAT) of rats exposed to cold or treated with 2.25% l-arginine for 1, 3, and 7 days. Compared to untreated control, levels of inducible nitric oxide (NO) synthase protein expression and NO signaling increased in both cold-exposed and l-arginine-treated groups. These increases coincided with the appearance of multilocular adipocytes and increased expression levels of uncoupling protein 1 (UCP1), thermogenic and beige adipocyte-specific genes (Cidea, Cd137, and Tmem26), mitochondriogenesis markers (peroxisome proliferator-activated receptor (PPAR)-gamma coactivator-1 alpha, mitochondrial DNA copy number), nuclear respiratory factor 1, PPAR alpha and their respective downstream lipid oxidation enzymes after l-arginine treatment. Such browning phenotype in the l-arginine-treated group was concordant with end-course decreases in leptinaemia, rpWAT mass, and body weight. In conclusion, l-arginine mimics cold-mediated increases in NO signaling in rpWAT and induces molecular and structural fingerprints of rpWAT browning. The results endorse l-arginine as a pharmaceutical alternative to cold exposure, which could be of great interest in obesity and associated metabolic diseases.
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