Fasting upregulates adipose triglyceride lipase and hormone-sensitive lipase levels and phosphorylation in mouse kidney
Abstract
Circulating non-esterified fatty acids (NEFA) rise during fasting and are taken up by the kidneys, either directly from the plasma or during re-uptake of albumin from glomerular filtrate, and are stored as triacylglycerol (TAG). Subsequent utilization of stored fatty acids requires their hydrolytic release from cellular lipid droplets, but relatively little is known about renal lipolysis. We found that total [3H]triolein hydrolase activity of kidney lysates was significantly increased by 15% in the fasted state. Adipose triglyceride lipase (Atgl) and hormone-sensitive lipase (Hsl) mRNA expression was time-dependently increased by fasting, along with other fatty acid metabolism genes (Pparα, Cd36, and Aox). ATGL and HSL protein levels were also significantly induced (by 239 ± 7% and 322 ± 8%, respectively). Concomitant with changes in total protein levels, there was an increase in ATGL phosphorylation at the AMPK-regulated serine 406 site in the 14-3-3 binding motif, and an increase in HSL phosphorylation at serines 565 and 660 that are regulated by AMPK and PKA, respectively. Using immunofluorescence, we further demonstrate nearly ubiquitous expression of ATGL in the renal cortex with a concentration on the apical/lumenal surface of some cortical tubules. Our findings suggest a role for ATGL and HSL in kidney lipolysis.
Résumé
Les acides gras non-estérifiés (AGNE) circulants augmentent durant le jeûne et ils sont captés par les reins, soit directement à partir du plasma, ou durant la recapture de l’albumine à partir du filtrat glomérulaire, pour être entreposés sous forme de triacylglycérol (TAG). L’utilisation subséquente des acides gras entreposés requiert leur libération hydrolytique des gouttelettes lipidiques cellulaires, mais on connaît peu de chose sur la lipolyse rénale. Les auteurs ont trouvé que l’activité [3H]trioléine hydrolase de lysats de rein était significativement accrue de 15% durant le jeûne. L’expression de l’ARNm de la triglycéride lipase des tissus adipeux (Atgl) et de la lipase hormono-sensible (Hsl) était accrue en fonction du temps durant le jeûne, parallèlement à celle d’autres gènes du métabolisme des acides gras (Pparα, Cd36 et Aox). Les niveaux protéiques d’ATGL et de HSL étaient aussi significativement accrus (de 239 ± 7% et 322 ± 8%, respectivement). De façon concomitante aux changements du niveau de protéines totales, la phosphorylation d’ATGL régulée par l’AMPK était accrue sur la sérine 406 du motif de liaison 14-3-3, de même que la phosphorylation de HSL sur les sérines 565 et 660 qui sont respectivement régulées par l’AMPK et la PKA. À l’aide de l’immunofluorescence, les auteurs ont de plus démontré l’expression presque ubiquiste d’ATGL dans le cortex rénal, avec une concentration à la surface apicale/luminale de certains tubules corticaux. Leurs données suggèrent qu’ATGL et HSL jouent un rôle dans la lipolyse rénale. [Traduit par la Rédaction]
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Biochemistry and Cell Biology
Volume 93 • Number 3 • June 2015
Pages: 262 - 267
History
Received: 7 November 2014
Revision received: 5 March 2015
Accepted: 17 March 2015
Accepted manuscript online: 30 March 2015
Version of record online: 30 March 2015
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© 2015.
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Phillip M. Marvyn, Ryan M. Bradley, Emily B. Button, Emily B. Mardian, and Robin E. Duncan. 2015. Fasting upregulates adipose triglyceride lipase and hormone-sensitive lipase levels and phosphorylation in mouse kidney. Biochemistry and Cell Biology.
93(3): 262-267. https://doi.org/10.1139/bcb-2014-0150
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