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AMPK in the gut-liver-brain axis and its influence on OP rats in an HSHF intake and WTD rat model


Obesogenic diets (ODs) can affect AMPK activation in several sites as the colon, liver, and hypothalamus. OD intake can impair the hypothalamic AMPK regulation of energy homeostasis. Despite consuming ODs, not all subjects have the propensity to develop or progress to obesity. The obesity propensity is more associated with energy intake than expenditure dysregulations and may have a link with AMPK activity. While the effects of ODs are studied widely, few evaluate the short-term effects of terminating OD intake. Withdrawing from OD (WTD) is thought to improve or reverse the damages caused by the intake. Therefore, here we applied an OD intake and WTD protocol aiming to evaluate AMPK protein content and phosphorylation in the colon, liver, and hypothalamus and their relationship with obesity propensity. To this end, male Wistar rats (60 days) received control or high-sugar/high-fat (HSHF) OD for 30 days. Half of the animals were OD-withdrawn and fed the control diet for 48 h. After intake, we found a reduction in AMPK phosphorylation in the hypothalamus and colon, and after WTD, we found an increase in its hepatic and hypothalamic phosphorylation. The decrease in colon pAMPK/AMPK could be linked with hypothalamic pAMPK/AMPK after HSHF intake, while the increase in hepatic pAMPK/AMPK could have prevented the increase in hypothalamic pAMPK/AMPK. In the obesity-prone rats, we found higher levels of hypothalamic and colon pAMPK/AMPK despite the higher body mass gain. Our results highlight the relevance in multi-organ investigations and animal phenotype evaluation when studying the energy metabolism regulations.

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This work was supported in part by the “Coordination for the Improvement of Higher Education Personnel” (CAPES Brazil—Financial Code 001) and by the “São Paulo Research Foundation” (FAPESP #2017/25420-3). LPP is a beneficiary of the “National Council for Scientific and Technological Development” (CNPq) productivity fellowship. BPC is a Ph.D. scholarship recipient from FAPESP (#2019/22511-3).

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BPC: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, roles/writing (original draft), and writing (review and editing).

LPP: Conceptualization, funding acquisition, investigation, methodology, resources, supervision, and writing (review and editing).

DE: Conceptualization, data curation, formal analysis, funding acquisition, investigation, methodology, project administration, resources, supervision, and writing (review and editing).

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Correspondence to Debora Estadella.

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Casagrande, B.P., Pisani, L.P. & Estadella, D. AMPK in the gut-liver-brain axis and its influence on OP rats in an HSHF intake and WTD rat model. Pflugers Arch - Eur J Physiol 473, 1199–1211 (2021).

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  • AMPK
  • Hypothalamus
  • Colon
  • Liver
  • Withdrawal