Ghoshal Sarbani, Mukherjee Sandip, Chakraborty Molee, Msengi Eliwaza Naomi, Haubner Jake, Chakraborty Anutosh
Department of Metabolism and Aging, The Scripps Research Institute, Jupiter, FL 33458, USA.
Department of Biological Sciences and Geology, QCC-City University of New York, New York, NY 11364, USA.
Int J Mol Sci. 2022 Feb 12;23(4):2059. doi: 10.3390/ijms23042059.
(1) Background: We previously demonstrated that disruption of IP6K1 improves metabolism, protecting mice from high-fat diet-induced obesity, insulin resistance, and non-alcoholic fatty liver disease and steatohepatitis. Age-induced metabolic dysfunction is a major risk factor for metabolic diseases. The involvement of IP6K1 in this process is unknown. (2) Methods: Here, we compared body and fat mass, insulin sensitivity, energy expenditure and serum-, adipose tissue- and liver-metabolic parameters of chow-fed, aged, wild type () and whole body knockout () mice. (3) Results: IP6K1 was upregulated in the adipose tissue and liver of mice compared to young mice. Moreover, deletion blocked age-induced increase in body- and fat-weight and insulin resistance in mice. mice oxidized carbohydrates more efficiently. The knockouts displayed reduced levels of serum insulin, triglycerides, and non-esterified fatty acids. deletion partly protected age-induced decline of the thermogenic uncoupling protein UCP1 in inguinal white adipose tissue. Targets inhibited by IP6K1 activity such as the insulin sensitivity- and energy expenditure-inducing protein kinases, protein kinase B (PKB/Akt) and AMP-activated protein kinase (AMPK), were activated in the adipose tissue and liver of mice. (4) Conclusions: deletion maintains healthy metabolism in aging and thus, targeting this kinase may delay the development of age-induced metabolic dysfunction.
(1) 背景：我们之前证明，IP6K1的缺失可改善新陈代谢，保护小鼠免受高脂饮食诱导的肥胖、胰岛素抵抗、非酒精性脂肪性肝病和脂肪性肝炎的影响。年龄诱导的代谢功能障碍是代谢性疾病的主要危险因素。IP6K1在此过程中的作用尚不清楚。(2) 方法：在此，我们比较了正常饮食喂养的老年野生型（）和全身敲除（）小鼠的体重、脂肪量、胰岛素敏感性、能量消耗以及血清、脂肪组织和肝脏的代谢参数。(3) 结果：与年轻小鼠相比，老年小鼠脂肪组织和肝脏中IP6K1上调。此外，敲除可阻止小鼠年龄诱导的体重和脂肪量增加以及胰岛素抵抗。小鼠能更有效地氧化碳水化合物。敲除小鼠血清胰岛素、甘油三酯和非酯化脂肪酸水平降低。敲除部分保护了腹股沟白色脂肪组织中年龄诱导的产热解偶联蛋白UCP1的下降。IP6K1活性抑制的靶点，如诱导胰岛素敏感性和能量消耗的蛋白激酶蛋白激酶B（PKB/Akt）和AMP激活的蛋白激酶（AMPK），在敲除小鼠的脂肪组织和肝脏中被激活。(4) 结论：敲除可维持衰老过程中的健康代谢，因此，靶向这种激酶可能会延缓年龄诱导的代谢功能障碍的发展。
