Key result
Liraglutide increased type 2 deiodinase activity and oxygen consumption in brown adipose tissue, and enhanced beta3-adrenergic-induced thermogenesis in obese mice.
Why the study?
Although liraglutide-induced weight loss is attributed to appetite suppression, therapy may also increase energy expenditure through GLP-1 signaling in thermogenic fat.
Does liraglutide increase adipose tissue oxygen consumption and type 2 deiodinase activity in male C57BL/6J mice?
Does liraglutide increase adipose tissue oxygen consumption and type 2 deiodinase activity in male C57BL/6J mice?
Liraglutide enhances thermogenesis and increases type 2 deiodinase activity in brown adipose tissue, suggesting a novel mechanism for GLP-1 receptor agonist-induced weight loss.
Liraglutide effects on murine thermogenesis remain preclinical; leaves open human energy-expenditure relevance.
Aims: Liraglutide is a long-acting glucagon-like peptide 1 (GLP-1) receptor agonist used as an anti-hyperglycemic agent in type 2 diabetes treatment and recently approved for obesity management. Weight loss is attributed to appetite suppression, but therapy may also increase energy expenditure. To further investigate the effect of GLP-1 signaling in thermogenic fat, we assessed adipose tissue oxygen consumption and type 2 deiodinase (D2) activity in mice treated with liraglutide, both basally and after β3-adrenergic treatment. Methods: Male C57BL/6J mice were randomly assigned to receive liraglutide (400 μg/kg, n=12) or vehicle (n=12). After 16 days, mice in each group were co-treated with the selective β3-adrenergic agonist CL316,243 (1 mg/kg, n=6) or vehicle (n=6) for 5 days. Adipose tissue depots were assessed for gene and protein expression, oxygen consumption, and D2 activity. Results: Liraglutide increased interscapular brown adipose tissue (iBAT) oxygen consumption and enhanced β3-adrenergic-induced oxygen consumption in iBAT and inguinal white adipose tissue (ingWAT). These effects were accompanied by upregulation of UCP-1 protein levels in iBAT and ingWAT. Notably, liraglutide increased D2 activity without significantly upregulating its mRNA levels in iBAT and exhibited additive effects to β3-adrenergic stimulation in inducing D2 activity in ingWAT. Conclusions: Liraglutide exhibits additive effects to those of β3-adrenergic stimulation in thermogenic fat and increases D2 activity in BAT, implying that it may activate this adipose tissue depot by increasing intracellular thyroid activation, adding to the currently known mechanisms of GLP-1A-induced weight loss.
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Oliveira et al. (2022) studied Obesity (diet-induced) (n=24). Liraglutide vs. Vehicle (saline) was evaluated on Type 2 deiodinase (D2) activity and oxygen consumption in adipose tissue. Liraglutide increased type 2 deiodinase activity and oxygen consumption in brown adipose tissue, and enhanced beta3-adrenergic-induced thermogenesis in obese mice.
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