3-hydroxymorphinan enhances mitochondrial biogenesis and adipocyte browning through AMPK-dependent pathway

Area of Science:

• Metabolism
• Cell Biology
• Pharmacology

Background:

• 3-hydroxymorphinan (3-HM), a dextromethorphan metabolite, shows anti-inflammatory, antioxidant, and neuroprotective effects.
• The impact of 3-HM on adipocyte energy metabolism is not well understood.

Purpose of the Study:

• To investigate the effects of 3-HM on mitochondrial biogenesis, oxidative stress, and lipid accumulation in 3T3-L1 adipocytes.
• To explore the molecular mechanisms underlying 3-HM's actions in adipocytes.

Main Methods:

• 3T3-L1 adipocytes were treated with 3-HM.
• Protein expression was analyzed using western blotting.
• Mitochondrial and lipid accumulation were assessed via staining; cell toxicity was evaluated.
• AMPK signaling was investigated using siRNA.

Main Results:

• 3-HM increased brown adipocyte markers (UCP-1, PGC-1α) and promoted mitochondrial biogenesis.
• 3-HM suppressed mitochondrial ROS and superoxide generation, enhancing mitochondrial complex I activity.
• 3-HM treatment enhanced AMPK phosphorylation, which was reversed by AMPK suppression.

Conclusions:

• 3-HM promotes mitochondrial biogenesis and adipocyte browning.
• 3-HM attenuates oxidative stress and lipid accumulation in adipocytes through AMPK signaling.
• 3-HM-mediated AMPK activation presents a potential therapeutic strategy for obesity and related metabolic diseases.