<span style="font-variant: small-caps">l</span>-Arginine Induces White Adipose Tissue Browning-A New Pharmaceutical Alternative to Cold

• Main Authors: Andjelika Kalezic (Author), Aleksandra Korac (Author), Bato Korac (Author), Aleksandra Jankovic (Author)
• Format: Book
• Published: MDPI AG, 2022-06-01T00:00:00Z.
• Subjects: article
• Online Access: Connect to this object online.
• Notes: 10.3390/pharmaceutics14071368; 1999-4923
• Keywords: nitric oxide; <span style="font-variant: small-caps">l-</span>arginine; browning; obesity; Pharmacy and materia medica; RS1-441
• Source: Pharmaceutics, Vol 14, Iss 7, p 1368 (2022)

The beneficial effects of <span style="font-variant: small-caps;">l-</span>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 <span style="font-variant: small-caps;">l-</span>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% <span style="font-variant: small-caps;">l-</span>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 <span style="font-variant: small-caps;">l-</span>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 (<i>Cidea</i>, <i>Cd137</i>, and <i>Tmem26</i>), mitochondriogenesis markers (peroxisome proliferator-activated receptor (PPAR)-γ coactivator-1α, mitochondrial DNA copy number), nuclear respiratory factor 1, PPARα and their respective downstream lipid oxidation enzymes after <span style="font-variant: small-caps;">l-</span>arginine treatment. Such browning phenotype in the <span style="font-variant: small-caps;">l-</span>arginine-treated group was concordant with end-course decreases in leptinaemia, rpWAT mass, and body weight. In conclusion, <span style="font-variant: small-caps;">l-</span>arginine mimics cold-mediated increases in NO signaling in rpWAT and induces molecular and structural fingerprints of rpWAT browning. The results endorse <span style="font-variant: small-caps;">l-</span>arginine as a pharmaceutical alternative to cold exposure, which could be of great interest in obesity and associated metabolic diseases.