C12TPP – (17895-72-6)

Dodecyltriphenylphosphonium (C12TPP), a mitochondria-targeted compound, has demonstrated significant potential in combating high-fat-diet-induced obesity in mice. This cationic molecule facilitates the recycling of fatty acids in both artificial lipid membranes and mitochondria, effectively dissipating the mitochondrial membrane potential. This process can influence total energy expenditure and body weight in animals and humans.

In a study conducted at thermoneutrality, mice treated with C12TPP (50 µmol per day per kg body weight) in their drinking water experienced a significant reduction in body weight (12%) and body fat mass (24%) within the first seven days. The treatment did not affect water palatability or intake, nor did it alter the energy and lipid content in feces. C12TPP increased oxygen consumption in isolated brown-fat mitochondria and enhanced oligomycin-insensitive oxygen consumption in brown adipocyte cultures. These effects were independent of uncoupling protein 1 (UCP1), although C12TPP treatment increased mitochondrial protein levels in the brown adipose tissue of both wild-type and UCP1-knockout mice.

The study revealed that C12TPP combats diet-induced obesity through multiple mechanisms: it reduces food intake, increases the resting metabolic rate (RMR) by up to 18%, and enhances fatty acid oxidation. The reduction in food intake was temporary, with spontaneous restoration after the initial treatment period. Importantly, the body weight loss in C12TPP-treated mice was not solely due to decreased food intake; pair-feeding experiments indicated that only one-third of the weight loss was attributable to reduced food intake, suggesting that the majority of the effect was due to increased energy expenditure.

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Sources:

https://pubchem.ncbi.nlm.nih.gov/compound/84956
https://www.nature.com/articles/ijo2016146
https://www.sciencedirect.com/science/article/abs/pii/S0024320521011619