Deletion of GABABR in Kiss1 cells affects GLUCOSE HOMEOSTASIS in young adult male mice.

DI GIORGIO NP; BIZZOZZERO HIRIART, MARIANNE; SURKIN, PABLO N.; REPETTO, E; BETTLER B; LIBERTUN C; LUX LANTOS V

Congreso; Kisspeptin Virtual Meeting; 2021

Kisspeptin + 2021 Virtual Conference

DELETION OF GABABR IN KISS1 CELLS AFFECTS GLUCOSE HOMEOSTASIS IN YOUNG ADULT MALE MICE.Noelia P. Di Giorgio1*, Marianne Bizzozzero Hiriart 1, Pablo N. Surkin 1, Esteban Repetto1, Bernhard Bettler 2, Carlos Libertun 1, Victoria A. Lux-Lantos 1. 1 Laboratory of Neuronendocrinology, IBYME-CONICET, Buenos Aires, Argentina. 2 University of Basel, Switzerland. *contact e-mail: ndigiorgio@ibyme.conicet.gov.arKisspeptin (encoded by Kiss1 gene) neurons co-express GABAB receptors (GABABR) and GABA is an important regulator of their physiology. Kiss1 expression is a key factor in the control of reproduction and is involved in metabolic control. We developed a new strain of mice with specific deletion of GABAB1R in Kiss1 cells/neurons (KO). KO males have similar body weight compared to WT from birth to adulthood; however, they have an increase in postnatal ano-genital index (AGI) between PND7 and PND21. Here, we confirm the specific deletion of GABAB1R by double immunofluorescence and we evaluate the neuroendocrine/reproductive axis and different parameters of glucose homeostasis in WT and KO young adult males: a) AGI, hormonal levels and fertility; b) Kiss1 expression in hypothalamic/extra-hypothalamic nuclei and testis; c) non-fasted (NFG) and fasted (FG) glycaemia; d) glucose (GTT) and insulin (ITT) tolerance tests. We found that AGI, LH, testosterone levels and fertility were similar between genotypes. However, we found that Kiss1 was increased in testis without differences in arcuate nucleus or medial amigdala. On the other hand, while KO males had normal NFG, they had higher FG, altered response to glucose overload (GTT) and lower insulin sensitivity (ITT). In conclusion, prebubertal AGI and adult Kiss1 expression alteration in testis do not impact on fertility. However, the lack of GABABR in Kiss1 cells alters glucose homeostasis in young adult male mice. We need to investigate whether these alterations have a central or peripheral origin, or both. (CONICET/ANPCYT/ISN-CAEN/UBA/René Barón F/Williams F.)