Maternal obesity promotes impaired renal autophagic process and kidney injury in male offspring.

IF 4.2 2区 医学 Q1 ENDOCRINOLOGY & METABOLISM
Nichakorn Phengpol, Sasivimon Promsan, Nattavadee Pengrattanachot, Onanong Jaruan, Prempree Sutthasupha, Anusorn Lungkaphin
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Abstract

Background: Obesity during pregnancy increases the risk of obesity, insulin resistance, diabetes, and the development and progression of chronic kidney disease (CKD) in later life in offspring. Impaired renal autophagic process is linked to kidney dysfunction in the setting of increased renal lipid accumulation. The aim of this study was to elucidate the effect of maternal obesity on kidney injury related to impaired renal autophagic process in the offspring.

Methods: Maternal obesity model was conducted using female C57BL/6 mice fed with high-fat diet (HFD) for 8 weeks before mating. HFD was consecutively maintained throughout gestation and lactation. Male offspring were selected for investigation after weaning. Metabolic parameters and kidney morphology were performed. Renal insulin signaling, lipid metabolism, lipid accumulation, fibrosis and autophagy were determined.

Results: Male offspring of HFD fed mothers developed obesity with insulin resistance, hyperglycemia, hyperlipidemia and consequently promoted kidney injury. Maternal obesity increased CD36, FAS, SREBP1c and Perilipin-2 while suppressed PPARα and CPT1A. The reduction of AMPK, SIRT1, Beclin-1, LC3B, and LAMP2 and the elevation of mTOR and SQSTM1/P62 were observed. These findings indicated the impairment of autophagy and renal lipid metabolism exaggerating renal lipid accumulation in the offspring of maternal obesity.

Conclusions: This study demonstrated that long-term HFD consumption in mothers promoted obesity with insulin resistance related kidney injury through the impairment of autophagic process and renal lipid metabolism in the offspring. These circumstances accelerated kidney injury and contributed to an increased susceptibility to CKD in male offspring of maternal obesity.

母亲肥胖可促进雄性后代肾自噬过程受损和肾损伤。
背景:孕期肥胖会增加后代日后肥胖、胰岛素抵抗、糖尿病和慢性肾脏疾病(CKD)发展和进展的风险。肾脏自噬过程受损与肾脂质积累增加的肾功能障碍有关。本研究的目的是阐明母亲肥胖对后代肾自噬过程受损相关肾损伤的影响。方法:雌性C57BL/6小鼠在交配前8周饲喂高脂饲料(HFD),建立母鼠肥胖模型。HFD在整个妊娠期和哺乳期持续维持。选取断奶后的雄性子代进行调查。观察代谢参数和肾脏形态。测定肾脏胰岛素信号、脂质代谢、脂质积累、纤维化和自噬。结果:HFD喂养母鼠的雄性后代出现肥胖、胰岛素抵抗、高血糖、高脂血症,从而促进肾损伤。产妇肥胖增加CD36、FAS、SREBP1c和Perilipin-2,抑制PPARα和CPT1A。AMPK、SIRT1、Beclin-1、LC3B和LAMP2的表达降低,mTOR和SQSTM1/P62的表达升高。这些发现表明,自噬和肾脏脂质代谢的损害加剧了母亲肥胖后代的肾脏脂质积累。结论:本研究表明,母亲长期食用HFD通过损害后代的自噬过程和肾脂质代谢,促进肥胖和胰岛素抵抗相关的肾损伤。这些情况加速了肾脏损伤,并导致母亲肥胖的男性后代对慢性肾病的易感性增加。
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来源期刊
International Journal of Obesity
International Journal of Obesity 医学-内分泌学与代谢
CiteScore
10.00
自引率
2.00%
发文量
221
审稿时长
3 months
期刊介绍: The International Journal of Obesity is a multi-disciplinary forum for research describing basic, clinical and applied studies in biochemistry, physiology, genetics and nutrition, molecular, metabolic, psychological and epidemiological aspects of obesity and related disorders. We publish a range of content types including original research articles, technical reports, reviews, correspondence and brief communications that elaborate on significant advances in the field and cover topical issues.
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