LIRAGLUTIDE REGULATES FATTY ACID STORAGE IN SERTOLI CELLS.

DASSO ME; CENTOLA CL; SORIA D; GALARDO MN; MERONI SB; RIERA MF

Congreso; LXVII REUNIÓN ANUAL DE LA SAIC; 2022

Sociedad Argentina de Investigación Clínica

Sertoli cells (SC) are necessary to provide the structural and nutritional support for germ cell development. SC convert glucose to lactate, the main energy substrate for spermatocytes and spermatids. Consequently, SC use fatty acids (FA) -stored as triacyglycerides (TAG) in lipid droplets (LD)- as its own energy source, being LD essentials to keep ATP levels. Obesity prevalence has risen dramatically and liraglutide (Lira), a glucagon-like peptide-1 analogue, has emerged as a useful drug for treatment of obesity and type 2 diabetes mellitus. It has been observed that Lira regulates cell metabolism in different cell types however, little is known about its possible effects on SC function. Considering that the regulation of FA storage may be relevant to seminiferous tubule physiology, the aim of this work was to study the effect of Lira on lipid storage in SC. For this purpose, SC cultures obtained from 20-day old rats were used. First, we determined that SC express GLP-1 receptor by RT-PCR. Then SC cultures were maintained under basal conditions (B) or incubated with Lira (100nM) for different period of time. We observed that Lira promotes an increase in LD number (B: 0.37±0.1; Lira:0.70 ±0.1*. means ± SD of number of LD per SC in one representative experiment out of three. *P < 0.05 vs B) that is accompanied by an increase in TAG content. Next, we analyzed the effects of Lira on the expression of proteins involved in FA storage such as FAT/CD36 -a FA transporter- and glycerol-phosphate-acyl-transferases 1 and 4-GPAT1 and 4 enzymes involved in TAGs synthesis- by RT-qPCR. We observed that Lira increases FAT/CD36 mRNA levels after 6h of treatment (2.0±0.3* fold variation vs. B). Taken together, these results suggest that Lira can modulate lipid storage, which is essential to sustain SC energetic metabolism. (PICT2020-0642; PIP2021-162).