Key result
Nanocarrier-delivered glucocorticoid receptor agonists reduce body weight and fat without altering food intake in mice.
Why the study?
Obesity carries risk for cardiovascular diseases and type 2 diabetes linked to adipose tissue inflammation, an axis not targeted directly by current therapies.
Does delivery of an anti-inflammatory glucocorticoid receptor agonist via dextran nanocarriers reduce body weight and fat in a mouse model of obesity?
Does delivery of an anti-inflammatory glucocorticoid receptor agonist via dextran nanocarriers reduce body weight and fat in a mouse model of obesity?
Targeting adipose tissue macrophages with nanocarrier-delivered glucocorticoid receptor agonists reduces body weight and fat in obese mice without suppressing food intake.
Obesity is a risk factor for high-mortality health conditions, including cardiovascular diseases and type 2 diabetes, which makes the advancement of efficacious and safe weight loss therapies a high priority in pharmacology. The causal link between obesity and its comorbid conditions is believed to be a chronic state of inflammation originating within adipose tissue, with macrophages playing central roles, an axis that is not targeted directly by current therapies. Here, we use nanocarriers to deliver an anti-inflammatory glucocorticoid receptor agonist to adipose tissue macrophages and report the impact of size on therapeutic effect. Three dextran nanocarriers between 4–30 nm in hydrodynamic diameter released molecular drug cargo at equivalent rates and exhibited similar biological potency in vitro. In vivo in a mouse model of obesity, body weight and body fat were reduced in a size-dependent manner after 2–4 weeks of treatment. Unlike current clinical pharmacotherapies for weight loss, these body composition changes were not associated with changes in food intake. Greater retention of larger dextran nanocarriers in visceral adipose tissue appears to elicit a local change to promote browning by increasing mitochondrial abundance and lipid droplet fragmentation. Further development of this platform may result in a safe and potent modulator of adipose tissue in the state of obesity without direct action on nutrient intake to address malnutrition and lean body mass deficiencies observed with current weight loss pharmacotherapies.
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Medina et al. (2026) studied Obesity. Dextran nanocarriers delivering an anti-inflammatory glucocorticoid receptor agonist was evaluated on Body weight and body fat. Treatment with 4-30 nm dextran nanocarriers delivering a glucocorticoid receptor agonist for 2-4 weeks reduced body weight and fat in a size-dependent manner without changing food intake in mice.
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