Hepatic glycogen participates in the regulation of hypothalamic pAkt/Akt ratio in high-sugar/high-fat diet-induced obesity.
Metab Brain Dis
; 37(5): 1423-1434, 2022 06.
Article
em En
| MEDLINE
| ID: mdl-35316448
ABSTRACT
The hypothalamus is a major integrating centre that controls energy homeostasis and plays a major role in hepatic glycogen (HGlyc) turnover. Not only do hypothalamic and hepatic Akt levels influence glucose homeostasis and glycogen synthesis, but exposure to high-sugar/high-fat diets (HSHF) can also lead to hypothalamic inflammation and HGlyc accumulation. HSHF withdrawal overall restores energy and glucose homeostasis, but the actual relationship between hypothalamic inflammation and HGlyc after short-term HSHF withdrawal has not yet been fully elucidated. Here we investigated the short-term effects of HSHF withdrawal preceded by a 30-day HSHF intake on the liver-hypothalamus crosstalk and glucose homeostasis. Sixty-day old male Wistar rats were fed for 30 days a control chow (n = 10) (Ct), or an HSHF diet (n = 20). On the 30th day of dietary intervention, a random HSHF subset (n = 10) had their diets switched to control chow for 48 h (Hw) whilst the remaining HSHF rats remained in the HSHF diet (n = 10) (Hd). All rats were anaesthetized and euthanized at the end of the protocol. We quantified HGlyc, Akt phosphorylation, inflammation and glucose homeostasis biomarkers. We also assessed the effect of propensity to obesity on those biomarkers, as detailed previously. Hd rats showed impaired glucose homeostasis, higher HGlyc and hypothalamic inflammation, and lower pAkt/Akt. Increased HGlyc was significantly associated with HSHF intake on pAkt/Akt lowered levels. We also found that HGlyc breakdown may have prevented a further pAkt/Akt drop after HSHF withdrawal. Propensity to obesity showed no apparent effect on hypothalamic inflammation or glucose homeostasis. Our findings suggest a comprehensive role of HGlyc as a structural and functional modulator of energy metabolism, and such roles may come into play relatively rapidly.
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Base de dados:
MEDLINE
Assunto principal:
Dieta Hiperlipídica
/
Glicogênio Hepático
Idioma:
En
Revista:
Metab Brain Dis
Ano de publicação:
2022
Tipo de documento:
Article
País de afiliação:
Brasil