RT Journal Article
T1 Increased FGF21 in brown adipose tissue of tyrosine hydroxylase heterozygous mice: implications for cold adaptation
A1 Hernández Sánchez, Catalina
A1 Escalona Garrido, Carmen
A1 Pereira, Laura
A1 Contreras Jiménez, Cristina
A1 López, Miguel
A1 Balsinde, Jesús
A1 De Pablo, Flora
A1 Martínez Valverde, Ángela María
AB Tyrosine hydroxylase (TH) catalyzes the first step in catecholamines synthesis. We studied the impact of reduced TH in brown adipose tissue (BAT) activation. In adult heterozygous (Th+/- ) mice, dopamine and noradrenaline (NA) content in BAT decreased after cold exposure. This reduced catecholaminergic response did not impair cold adaptation, because these mice induced uncoupling protein 1 (UCP-1) and maintained BAT temperature to a similar extent than controls (Th+/+ ). Possible compensatory mechanisms implicated were studied. Prdm16 and Fgf21 expression, key genes in BAT activation, were elevated in Th+/- mice at thermoneutrality from day 18.5 of embryonic life. Likewise, plasma FGF21 and liver Fgf21 mRNA were increased. Analysis of endoplasmic reticulum (ER) stress, a process that triggers elevations in FGF21, showed higher phospho-IRE1, phospho-JNK, and CHOP in BAT of Th+/- mice at thermoneutrality. Also, increased lipolysis in BAT of cold-exposure Th+/- mice was demonstrated by increased phosphorylation of hormone-sensitive lipase (HSL), as well as diacylglycerol (DAG) and FFA content. Overall, these results indicate that the mild effects of Th haploinsufficiency on BAT function are likely due to compensatory mechanisms involving elevations in Fgf21 and Prdm16 and through adaptive changes in the lipid profile.
PB Elsevier
SN 0022-2275
YR 2018
FD 2018-10-23
LK https://hdl.handle.net/20.500.14352/112139
UL https://hdl.handle.net/20.500.14352/112139
LA eng
NO Vázquez P, Hernández-Sánchez C, Escalona-Garrido C, Pereira L, Contreras C, López M, Balsinde J, de Pablo F, Valverde ÁM. Increased FGF21 in brown adipose tissue of tyrosine hydroxylase heterozygous mice: implications for cold adaptation. J Lipid Res. 2018 Dec;59(12):2308-2320. doi: 10.1194/jlr.M085209
DS Docta Complutense
RD 11 abr 2025