Deficiency of Adipose Aryl Hydrocarbon Receptor Protects against Diet-Induced Metabolic Dysfunction through Sexually Dimorphic Mechanisms.
Deficiency of Adipose Aryl Hydrocarbon Receptor Protects against Diet-Induced Metabolic Dysfunction through Sexually Dimorphic Mechanisms.
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脂肪芳基烃受体的缺乏可通过性二态机制预防饮食诱导的代谢功能障碍。
DOI：
10.3390/cells12131748
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发表时间：
2023-06-29
期刊：
影响因子：
6
通讯作者：
Tischkau, Shelley A.
中科院分区：
文献类型：
--
作者：
Haque, Nazmul;Ojo, Emmanuel S.;Krager, Stacey L.;Tischkau, Shelley A.
关键词：
饮食诱导的肥胖症的分子机制是复杂的，仍然不清楚。芳香族烃受体（AhR），异生素传感器的激活，由肥胖可能有助于饮食诱导的肥胖，通过影响脂质代谢和胰岛素抵抗作用在各个部位，包括脂肪组织。因此，我们的假设是，条件性AhR消耗，特别是从成熟脂肪组织（CadKO），将改善高脂饮食（HFD）诱导的代谢功能障碍。CadKO保护小鼠免受HFD诱导的体重增加。CadKO女性摄入较少的卡路里，导致HFD的能量消耗（EE）增加和葡萄糖耐量改善。我们对脂肪组织生物学的探索表明，脂肪细胞中AhR的消耗为雌性小鼠提供了脂肪生成和脂肪分解的能力增加，从而维持健康的脂肪细胞表型。HFD诱导的瘦素升高在CadKO女性中减少，但下丘脑瘦素受体（LepR）在下丘脑的能量调节区中增加，表明对瘦素的敏感性增加。雌激素受体α（ERα）在CadKO雌性脂肪组织和下丘脑中较高。CadKO男性显示出肥胖和胰岛素抵抗的延迟进展。在雄性中，CadKO改善促炎性脂肪细胞因子分泌（如TNFα、IL 1 β、IL 6），并显示炎性巨噬细胞向脂肪库的浸润减少。总体而言，CadKO改善了HFD挑战下的体重控制和全身葡萄糖稳态，但在女性中的程度更深。CadKO促进女性的瘦表型，并介导健康的脂肪-下丘脑串扰。在男性中，脂肪特异性AhR耗竭通过维持脂肪细胞和免疫细胞之间的健康串扰来延迟肥胖和胰岛素抵抗的发展。
The molecular mechanisms underlying diet-induced obesity are complex and remain unclear. The activation of the aryl hydrocarbon receptor (AhR), a xenobiotic sensor, by obesogens may contribute to diet-induced obesity through influences on lipid metabolism and insulin resistance acting at various sites, including adipose tissue. Thus, our hypothesis was that conditional AhR depletion, specifically from mature adipose tissue (CadKO), would improve high-fat diet (HFD)-induced metabolic dysfunction. CadKO protects mice from HFD-induced weight gain. CadKO females eat fewer calories, leading to increased energy expenditure (EE) and improved glucose tolerance on HFD. Our exploration of adipose tissue biology suggests that the depletion of AhR from adipocytes provides female mice with an increased capacity for adipogenesis and lipolysis, allowing for the maintenance of a healthy adipocyte phenotype. The HFD-induced leptin rise was reduced in CadKO females, but the hypothalamic leptin receptor (LepR) was increased in the energy regulatory regions of the hypothalamus, suggesting an increased sensitivity to leptin. The estrogen receptor α (ERα) was higher in CadKO female adipose tissue and the hypothalamus. CadKO males displayed a delayed progression of obesity and insulin resistance. In males, CadKO ameliorated proinflammatory adipocytokine secretion (such as TNFα, IL1β, IL6) and displayed reduced inflammatory macrophage infiltration into adipose depots. Overall, CadKO improves weight control and systemic glucose homeostasis under HFD challenge but to a more profound extent in females. CadKO facilitates a lean phenotype in females and mediates healthy adipose–hypothalamic crosstalk. In males, adipose-specific AhR depletion delays the development of obesity and insulin resistance through the maintenance of healthy crosstalk between adipocytes and immune cells.
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影响因子：
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作者：
通讯作者：
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影响因子：
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作者：
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DOI：
10.1002/oby.21133
发表时间：
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期刊：
Obesity (Silver Spring, Md.)
影响因子：
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作者：
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影响因子：
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作者：
Jardí F;Laurent MR;Kim N;Khalil R;De Bundel D;Van Eeckhaut A;Van Helleputte L;Deboel L;Dubois V;Schollaert D;Decallonne B;Carmeliet G;Van den Bosch L;D'Hooge R;Claessens F;Vanderschueren D
通讯作者：
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影响因子：
2.6
作者：
Fierens, S;Mairesse, H;Bernard, A
通讯作者：
Bernard, A