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Characterization of inflammation and insulin resistance in high-fat diet-induced male C57BL/6J mouse model of obesity.

ABSTRACT: Background:Animal models of diet-induced obesity (DIO) are commonly used in medical research for mimicking human diseases. There is no universal animal model, and careful evaluation of variety of factors needs to be considered when designing new experiments. Here, we investigated the effect of 9 weeks high-fat diet (HFD) intervention, providing 60% energy from fat, on parameters of inflammation and insulin resistance in male C57BL/6J mice. Methods:Six weeks old mice were initiated on regular diet (RD) or HFD providing 60 kcal energy from fat for 9 weeks. Fasting blood glucose levels were measured by glucometer, and fasting plasma levels of insulin and proinflammatory cytokines by Luminex assay. Insulin sensitivity was evaluated by using QUICKI and HOMA2 indexes. Results:HFD mice showed ~ 40% higher body weight and ~ 20% larger abdominal circumference, due to an increase in the white adipose tissue mass. Liver examination revealed increased size and higher hepatic lipid accumulation in livers from HFD mice compared to their RD counterparts. Animals from the HFD group were characterized with significantly higher presence of crown-like structures (CLS) in WAT and higher plasma levels of proinflammatory cytokines (TNF-α, IL-6, leptin, MCP-1, PAI-1, and resistin). HFD-fed mice also demonstrated impaired insulin sensitivity (lower QUICKI, higher HOMA-insulin resistance (HOMA-IR), and lower HOMA-percent sensitivity (HOMA-%S)) index values. Conclusion:Male C57BL/6J mice on 9 weeks HFD providing 60 kcal energy from fat display impaired insulin sensitivity and chronic inflammation, thus making this DIO mouse model appropriate for studies of early stages of obesity-related pathology.

SUBMITTER: Avtanski D

PROVIDER: S-EPMC6930989 | biostudies-literature |

REPOSITORIES: biostudies-literature

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Project description:BackgroundTo date, there is only scare evidence characterizing the temporal features and progression of metabolic dysfunction in high-fat diet (HFD)-fed obese mice. Hence, its specific pathogenesis remains unclear.MethodsSixty 6-week-old male C57BL/6J mice were randomly divided into HFD and control diet (CD) groups and sacrificed at 1, 5, 9, 13, 17, and 21 weeks, respectively. At weekly intervals, intraperitoneal glucose tolerance testing (IPGTT) and intraperitoneal insulin tolerance testing (IPITT) were performed in both groups. A detailed time course in HFD-fed mice was investigated by evaluating the initiation of glucose homeostasis impairment, dyslipidemia, systemic insulin sensitivity, monocyte chemoattractant protein-1 (MCP-1) levels, epididymal white adipose tissue (eWAT) expansion, macrophage content changes, pro-inflammatory (M1)/anti-inflammatory (M2) macrophage imbalance, lipid accumulation in the liver, and β-cell morphometry in the pancreas.ResultsIn the HFD group, progressive weight gain and impairments in glucose metabolism (elevated fasting blood glucose and area under the curve (AUC) of IPGTT) were observed from the 3rd week, and a significantly elevated AUC of IPITT was first detected after week 7 of HFD feeding. As for dyslipidemia, after 9 weeks of feeding, the low-density lipoprotein cholesterol level and total cholesterol level in HFD group were significantly higher than those in the CD group (all P < 0.05), whereas no significant differences were shown in triglyceride level. Adipocyte size increased significantly in the HFD group in the 1st week, a phenotypic switch in eWAT from anti-inflammatory (M2) to pro-inflammatory (M1) macrophages was observed in the 5th week, and the metabolic inflammation was distinct in eWAT in the 9th week. Additionally, liver steatosis was considerably obvious at the 17th week and pancreatic β-cell morphometry did not change during 21 weeks of HFD feeding.ConclusionThe eWAT expansion was detected early in HFD-induced obese mice, which occurred prior to obvious insulin resistance.

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Characterization of inflammation and insulin resistance in high-fat diet-induced male C57BL/6J mouse model of obesity.

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