Department of Microbiology and Molecular Biology, Brigham Young University, Provo, UT 84602, USA.
Department of Physiology and Developmental Biology, Brigham Young University, Provo, UT 84602, USA.
Nutrients. 2018 Dec 15;10(12):1990. doi: 10.3390/nu10121990.
Diabetes and the related disease metabolic syndrome are epidemic in the United States, in part due to a shift in diet and decrease in physical exercise. PAS kinase is a sensory protein kinase associated with many of the phenotypes of these diseases, including hepatic triglyceride accumulation and metabolic dysregulation in male mice placed on a high-fat diet. Herein we provide the first characterization of the effects of western diet (high-fat high-sugar, HFHS) on Per-Arnt-Sim kinase mice (PASK) and the first characterization of both male and female PASK mice. Soleus muscle from the PASK male mice displayed a 2-fold higher oxidative phosphorylation capacity than wild type (WT) on the normal chow diet. PASK male mice were also resistant to hepatic triglyceride accumulation on the HFHS diet, displaying a 2.7-fold reduction in hepatic triglycerides compared to WT mice on the HFHS diet. These effects on male hepatic triglyceride were further explored through mass spectrometry-based lipidomics. The absence of PAS kinase was found to affect many of the 44 triglycerides analyzed, preventing hepatic triglyceride accumulation in response to the HFHS diet. In contrast, the female mice showed resistance to hepatic triglyceride accumulation on the HFHS diet regardless of genotype, suggesting the effects of PAS kinase may be masked.
糖尿病和相关的代谢综合征在美国流行，部分原因是饮食和体力活动的改变。PAS 激酶是一种与这些疾病的许多表型相关的感觉蛋白激酶，包括雄性小鼠高脂肪饮食引起的肝甘油三酯积累和代谢失调。本文首次描述了高脂肪高糖饮食（HFHS）对 Per-Arnt-Sim 激酶（PASK）小鼠的影响，以及对雄性和雌性 PASK 小鼠的首次描述。在正常饲料中，PASK 雄性小鼠的比目鱼肌的氧化磷酸化能力比野生型（WT）高 2 倍。在 HFHS 饮食中，PASK 雄性小鼠对肝甘油三酯积累也有抗性，与 HFHS 饮食中的 WT 小鼠相比，肝甘油三酯减少了 2.7 倍。通过基于质谱的脂质组学进一步研究了男性肝甘油三酯的这些影响。发现 PAS 激酶的缺失会影响分析的 44 种甘油三酯中的许多种，从而阻止肝甘油三酯在 HFHS 饮食中的积累。相比之下，无论基因型如何，雌性小鼠在 HFHS 饮食中都表现出对肝甘油三酯积累的抗性，这表明 PAS 激酶的作用可能被掩盖。
