Endocrine Abstracts

Brown adipocytes dissipate energy through the production of heat, acting as a defense against cold and obesity, and secrete batokines, that positively regulate metabolic functions. Thus, identifying brown-promoting molecules is crucial for developing novel therapeutic strategies against obesity and metabolic disorders. Of note, differentiation into myoblasts and later myocytes of myogenic factor 5 (Myf5) positive progenitors, the same from which brown adipocytes originate, is controlled by several transcription factors, such as Myf5, myogenic differentiation 1 (MyoD1), myogenin (MyoG) and myogenic regulatory factor 4 (MRF4). Moreover, different compounds can induce myoblasts to transdifferentiate into non-muscle cells, including brown adipocytes. Similarly, in response to different stimuli, white preadipocytes transdifferentiate into beige adipocytes, morphologically and functionally similar to brown adipocytes. Growth hormone-releasing hormone (GHRH), a hypothalamic neuropeptide that regulates synthesis and secretion of pituitary growth hormone (GH), exerts peripheral effects through binding to GHRH receptor (GHRH-R), expressed in many extrapituitary tissues, including adipocytes and skeletal muscle cells. Although studies have shown that GHRH counteracts skeletal muscle atrophy and ameliorates dyslipidaemia, its role in browning remains unknown. Thus, we evaluated the role of GHRH in transdifferentiation of murine C2C12 myoblasts and 3T3-L1 preadipocytes into brown/beige adipocytes. C2C12 myoblasts were treated with brown adipogenic differentiation medium for 7 days, in either absence or presence of GHRH (0.1 and 0.5 μM). Instead, 3T3-L1 preadipocytes were first differentiated into white adipocytes for 10 days (in whitening medium), then transdifferentiated for 72 h into beige adipocytes (in browning medium), in either absence or presence of GHRH (0.5 and 1 μM). In C2C12 myoblasts, GHRH (0.5 μM) suppressed the mRNA expression of myogenic markers MyoD1, MyoG, Myf5 and MRF4, whilst increasing brown/beige genes UCP1, PGC-1α, PRMD16, DIO2, CIDEA, Tmem26 and CD137. These results were confirmed by a decrease in protein levels of MyoG and increase in UCP1, PGC-1α and PRMD16. Similarly, in 3T3-L1 preadipocytes, GHRH (1 μM) increased mRNA and protein levels of brown/beige markers. Furthermore, in both cell types, Oil Red O staining showed that GHRH enhanced the number of small lipid droplets, characteristics of brown/beige adipocytes. Overall, these preliminary findings suggest that GHRH promotes transdifferentiation of both myoblasts and preadipocytes into beige/brown adipocytes, suggesting a potential therapeutic role in obesity and metabolic diseases.