Empagliflozin reverses obesity and insulin resistance through fat browning and alternative macrophage activation in mice fed a high-fat diet

Persistent inflammation reduces the liver's ability to respond to insulin, leading to increased blood sugar and fat buildup in the liver.

In obese mice on a high-fat diet, daily empagliflozin treatment for 8 weeks reduced body weight gain by 30% compared to untreated mice, due to higher energy expenditure and increased uncoupling protein 1 levels in fat tissues.

In obese mice fed a high-fat diet, 8 weeks of empagliflozin treatment increases insulin sensitivity, as measured by higher phosphorylation of Akt and insulin receptor β in fat, liver, and muscle tissues, and lower fasting insulin levels.

In obese mice fed a high-fat diet, empagliflozin treatment for 8 weeks decreased liver fat by 40%, reduced blood triglycerides and cholesterol, increased fatty acid oxidation, and decreased the activity of genes that produce fat, leading to less fatty liver disease.

In obese mice fed a high-fat diet, an 8-week course of empagliflozin changes the type of immune cells in fat and liver tissue from inflammatory to anti-inflammatory, leading to decreased inflammation and lower levels of inflammatory signaling molecules in the blood.

In obese mice fed a high-fat diet, a daily dose of empagliflozin for eight weeks raised levels of two anti-inflammatory signaling molecules in the blood and lowered levels of two pro-inflammatory signaling molecules, changing the overall pattern of fat-derived signaling molecules toward a less inflammatory state.