Effects of High Fat Diet on Metabolic Health Vary by Age of Menopause Onset.
Effects of High Fat Diet on Metabolic Health Vary by Age of Menopause Onset.
复制标题
高脂肪饮食对代谢健康的影响因更年期开始年龄而异。
DOI：
10.1101/2024.01.18.576269
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发表时间：
2024
期刊：
影响因子：
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通讯作者：
Zuloaga,KristenL
中科院分区：
文献类型：
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作者：
Salinero,AbigailE;Venkataganesh,Harini;Abi-Ghanem,Charly;Riccio,David;Kelly,RichardD;Gannon,OliviaJ;Sura,Avi;Brooks,HeddwenL;Zuloaga,KristenL
更年期会加速代谢功能障碍，包括(前驱)糖尿病、肥胖和内脏肥胖症。然而，内分泌和时序老化在这一过程中的作用还知之甚少。我们假设更年期，尤其是在中年的情况下，会加剧高脂肪饮食的代谢影响。我们使用年轻-成年和中年C57BL/6J雌性小鼠，通过长期给予高脂肪(HF)饮食和对照饮食来建立饮食诱导肥胖的模型。我们通过注射4-乙烯基环己烯二环氧化物来模拟围绝经期/绝经期，与赋形剂相比，4-乙烯基环己烯会加速卵巢衰竭。我们在饮食开始后2.5个月和7个月分别在围绝经期和绝经期进行了糖耐量测试。围绝经期增加了喂食HF的中年小鼠的葡萄糖耐量和体重增加的严重程度。更年期增加了所有小鼠的体重增加，无论年龄和饮食，而时间老化推动脂肪组织分布的变化更多的内脏脂肪而不是皮下脂肪。这些数据与显示绝经后女性更容易出现代谢功能障碍的临床数据一致，并表明年龄越大，内分泌老化(更年期)的影响就越严重。这项工作强调了在代谢健康研究中同时考虑时序和内分泌老化的重要性。
Menopause accelerates metabolic dysfunction, including (pre-)diabetes, obesity and visceral adiposity. However, the effects of endocrine vs. chronological aging in this progression are poorly understood. We hypothesized that menopause, especially in the context of middle-age, would exacerbate the metabolic effects of a high fat diet. Using young-adult and middle-aged C57BL/6J female mice, we modeled diet-induced obesity via chronic administration of high fat (HF) diet vs. control diet. We modeled peri-menopause/menopause via injections of 4-vinylcyclohexene diepoxide, which accelerates ovarian failure vs. vehicle. We performed glucose tolerance tests 2.5 and 7 months after diet onset, during the peri-menopausal and menopausal phases, respectively. Peri-menopause increased the severity of glucose intolerance and weight gain in middle-aged, HF-fed mice. Menopause increased weight gain in all mice regardless of age and diet, while chronological aging drove changes in adipose tissue distribution towards more visceral vs. subcutaneous adiposity. These data are in line with clinical data showing that post-menopausal women are more susceptible to metabolic dysfunction and suggest that greater chronological age exacerbates the effects of endocrine aging (menopause). This work highlights the importance of considering both chronological and endocrine aging in studies of metabolic health.