Apolipoprotein A-IV (apoA-IV), synthesized by enterocytes, is potentially involved in regulating lipid absorption and metabolism, food intake, and glucose metabolism. In this study, we backcrossed apoA-IV knockout (apoA-IV^−/−) mice onto the 129/SvJ background for eight generations. Compared to the wild-type (WT) mice, the 129/SvJ apoA-IV^−/− mice gained more weight and exhibited delayed glucose clearance even on the chow diet. During a 16-week high-fat diet (20% by weight of fat) study, apoA-IV^−/− mice were more obese than the WT mice, which was associated with their increased food intake as well as reduced energy expenditure and physical activity. In addition, apoA-IV^−/− mice developed significant insulin resistance (indicated by HOMA-IR) with severe glucose intolerance even though their insulin levels were drastically higher than the WT mice. In conclusion, we have established a model of apoA-IV^−/− mice onto the 129/SvJ background. Unlike in the C57BL/6J strain, apoA-IV^−/− 129/SvJ mice become significantly more obese and insulin-resistant than WT mice. Our current investigations of apoA-IV in the 129/SvJ strain and our previous studies in the C57BL/6J strain underline the impact of genetic background on apoA-IV metabolic effects.

Obesity is one of the main risk factors for cardiovascular diseases, type II diabetes, hypertension, and certain cancers. Obesity in women at the reproductive stage adversely affects contraception, fertility, maternal well-being, and the health of their offspring. Being a major protein component in chylomicrons and high-density lipoproteins, apolipoprotein A-IV (apoA-IV) is involved in lipid metabolism, food intake, glucose homeostasis, prevention against atherosclerosis, and platelet aggregation. The goal of the present study is to determine the impact of apoA-IV deficiency on metabolic functions in 129X1/SvJ female mouse strain. After chronic high-fat diet feeding, apoA-IV^−/− mice gained more weight with a higher fat percentage than wild-type (WT) mice, as determined by measuring their body composition. Increased adiposity and adipose cell size were also observed with a microscope, particularly in periovarian fat pads. Based on plasma lipid and adipokine assays, we found that obesity in apoA-IV^−/− mice was not associated with hyperlipidemia but with higher leptin levels. Compared to WT mice, apoA-IV deficiency displayed glucose intolerance and elevated insulin levels, according to the data of the glucose tolerance test, and increased HOMA-IR values at fasting, suggesting possible insulin resistance. Lastly, we found obesity in apoA-IV^−/− mice resulting from reduced energy expenditure but not food intake. Together, we established a novel and excellent female mouse model for future mechanistic study of obesity and its associated comorbidities.

Diabetic nephropathy (DN) is a prevalent and serious complication of diabetes, characterized by chronic inflammation and progressive kidney damage. This st