Cellular Longevity Inc., San Francisco, CA, USA.
Department of Clinical Studies - NBC, University of Pennsylvania School of Veterinary Medicine, Kennett Square, PA, USA.
Sci Rep. 2024 Jun 2;14(1):12639. doi: 10.1038/s41598-024-63373-5.
Chronic feeding of a high fat diet (HFD) in preclinical species induces broad metabolic dysfunction characterized by body weight gain, hyperinsulinemia, dyslipidemia and impaired insulin sensitivity. The plasma lipidome is not well characterized in dogs with HFD-induced metabolic dysfunction. We therefore aimed to describe the alterations that occur in the plasma lipid composition of dogs that are fed a HFD and examine the association of these changes with the clinical signs of metabolic dysfunction. Dogs were fed a normal diet (ND) or HFD for 12 weeks. Insulin sensitivity (S) and beta cell compensation (AIR) were assessed through an intravenous glucose tolerance test (IVGTT) and serum biochemistry was analyzed before the introduction of HFD and again after 12 weeks of continued ND or HFD feeding. Plasma lipidomics were conducted prior to the introduction of HFD and again at week 8 in both ND and HFD-fed dogs. 12 weeks of HFD feeding resulted in impaired insulin sensitivity and increased beta cell compensation measured by S (ND mean: 11.5 [mU/l] min, HFD mean: 4.7 [mU/l] min) and AIR (ND mean: 167.0 [mU/l]min, HFD mean: 260.2 [mU/l]min), respectively, compared to dogs fed ND over the same duration. Chronic HFD feeding increased concentrations of plasma lipid species and deleterious fatty acids compared to dogs fed a ND. Saturated fatty acid (SFA) concentrations were significantly associated with fasting insulin (R = 0.29), S (R = 0.49) and AIR (R = 0.37) in all dogs after 12 weeks, irrespective of diet. Our results demonstrate that chronic HFD feeding leads to significant changes in plasma lipid composition and fatty acid concentrations associated with metabolic dysfunction. High SFA concentrations may be predictive of deteriorated insulin sensitivity in dogs.
长期喂食高脂肪饮食（HFD）会导致广泛的代谢功能障碍，表现为体重增加、高胰岛素血症、血脂异常和胰岛素敏感性受损。患有 HFD 诱导的代谢功能障碍的犬的血浆脂质组学尚未得到很好的描述。因此，我们旨在描述喂食 HFD 的犬血浆脂质组成发生的变化，并研究这些变化与代谢功能障碍的临床症状之间的关联。犬喂食正常饮食（ND）或 HFD 12 周。通过静脉葡萄糖耐量试验（IVGTT）评估胰岛素敏感性（S）和β细胞补偿（AIR），并在引入 HFD 之前和继续喂食 12 周 ND 或 HFD 后分析血清生化指标。在引入 HFD 之前和 ND 或 HFD 喂养的犬的第 8 周再次进行血浆脂质组学检测。与喂食 ND 的犬相比，12 周的 HFD 喂养导致胰岛素敏感性受损和β细胞补偿增加，通过 S（ND 平均值：11.5 [mU/l] min，HFD 平均值：4.7 [mU/l] min）和 AIR（ND 平均值：167.0 [mU/l] min，HFD 平均值：260.2 [mU/l] min）测量。与喂食 ND 的犬相比，慢性 HFD 喂养会增加血浆脂质种类和有害脂肪酸的浓度。在所有 12 周后喂食 ND 的犬中，SFA 浓度与空腹胰岛素（R=0.29）、S（R=0.49）和 AIR（R=0.37）显著相关，与饮食无关。我们的结果表明，慢性 HFD 喂养会导致与代谢功能障碍相关的血浆脂质组成和脂肪酸浓度发生显著变化。高 SFA 浓度可能是犬胰岛素敏感性恶化的预测指标。
