BAM-15

BAM-15 is a mitochondrial uncoupler that increases energy expenditure by making cells burn more calories for the same amount of work. It boosts fat loss, improves insulin sensitivity, and helps rejuvenate mitochondrial function. Though not yet approved for human use, it has gained attention in anti-obesity and longevity research due to its ability to safely increase metabolic rate without stimulating the nervous system. BAM-15 is a synthetic small molecule that acts as a protonophore, disrupting the mitochondrial proton gradient to promote uncoupled respiration. Unlike earlier uncouplers like DNP, BAM-15 selectively increases mitochondrial inefficiency without generating excess heat or causing significant toxicity at therapeutic doses. Preclinical studies suggest it may be effective for reducing adiposity, improving insulin sensitivity, and protecting organs against metabolic damage and oxidative stress.

- Struggle with weight loss resistance or metabolic slowdown

- Experience fatigue or mitochondrial dysfunction

- Seek enhanced energy expenditure, fat oxidation, or metabolic flexibility

How this peptide works in the body

Mitochondrial Uncoupling via Protonophore Activity

• BAM-15 transports protons across the inner mitochondrial membrane independent of ATP synthase, collapsing the proton gradient without impairing electron transport. This leads to elevated oxygen consumption, increased substrate oxidation, and inefficient ATP production. The excess energy is released as mild heat, forcing the body to metabolize more fatty acids to maintain energy balance.

Stimulation of Fatty Acid Oxidation and Lipid Clearance

• BAM-15 activates AMPK due to lowered ATP/AMP ratio, promoting expression of CPT1, PPARα, and ACOX1, which enhance mitochondrial and peroxisomal β-oxidation. This reduces hepatic steatosis and serum triglycerides in obese models. Additionally, uncoupling increases the NAD+/NADH ratio, favoring catabolic metabolism and SIRT1 activation.

Improvement of Insulin Sensitivity and Glucose Metabolism

• BAM-15 reduces ectopic lipid accumulation in liver and muscle, alleviating lipotoxic insulin resistance. It enhances insulin receptor (INSR) phosphorylation and downstream Akt activation. This leads to improved GLUT4 translocation and glucose uptake, especially in skeletal muscle and adipose tissue.

Suppression of Mitochondrial ROS and Inflammatory Stress

• By lowering the mitochondrial membrane potential (ΔΨm), BAM-15 reduces electron leakage and ROS production at Complex I and III. It downregulates NF-κB and NLRP3 inflammasome activation, reducing levels of TNF-α and IL-6. This protects against oxidative damage in metabolic tissues and improves mitochondrial redox status.

Enhancement of Mitochondrial Biogenesis and Quality Control

• Chronic uncoupling with BAM-15 leads to upregulation of PGC-1α, NRF1, and TFAM, promoting mitochondrial biogenesis and DNA replication. It also stimulates mitophagy via PINK1/Parkin and enhances autophagy of damaged organelles, leading to a rejuvenated mitochondrial pool and improved metabolic efficiency.