Simultaneous pharmaceutical targeting of signalling pathways engaged by nicotine and cold exposure is demonstrated to lower body weight and improve metabolic health in mice in a study published in Nature Communications. The compounds icilin and dimethylphenylpiperazinium stimulate appetite suppressing and thermogenesis promoting pathways, which modulate whole body energy balance in order to promote weight loss in obese mice.

Obesity is a risk factor for metabolic diseases, such as diabetes, and presents a major health challenge. Tobacco smoking and cold exposure are environmental modulators of human energy metabolism, suppressing appetite and increasing energy expenditure respectively. Currently, pharmaceutical enhancement of thermogenesis (producing heat) is being pursued as a potential avenue to mimic cold exposure and increase energy expenditure thus promoting weight loss. However, an associated increase in food intake could counteract these effects.

Matthias Tschop and colleagues use a combinational therapy in which they simultaneously engage a nicotinic acetylcholine receptor called alpha3beta4 (α3β4) and a receptor that is activated in cold temperatures called transient receptor potential cation channel subfamily M member 8 (TRPM8) through small molecule therapy. The authors found that this treatment lowered body weight and corrected glucose intolerance in obese mice.

The findings open up a potential new therapeutic avenue for the treatment of obesity that does not bear the negative health consequences associated with cigarette smoke, the authors note. Further studies are required to determine if these findings translate to humans.