Work

Stimulation of soluble guanylyl cyclase protects against obesity by recruiting brown adipose tissue

Year: 2015

Type: article

Abstract: Clinical background Obesity has reached pandemic dimensions and novel pharmacological therapies are urgently needed. Obesity is characterized by excessive fat storage in white adipose tissue (WAT), because of a positive energy balance. In contrast to WAT, brown adipose tissue (BAT) dissipates energy and produces heat – a process known as nonshivering thermogenesis. To identify novel BATcentered antiobesity therapies, we studied the role of soluble guanylyl cyclase (sGC) in BAT. sGC produces the second messenger cyclic GMP (cGMP) after stimulation with nitric oxide. Here, we used a small molecule that stimulates sGC in a heme–dependent manner. Treatment of mice with the sGC stimulator during a high fat diet protected against weight gain and improved metabolic changes. Notably, stimulation of sGC induced weight loss also in already established obesity. Mechanistically, the sGC stimulator enhanced expression of thermogenic genes and induced “browning” (i.e. the expression of brown adipocytespecific markers) of murine and human adipocytes. sGC stimulation increased lipid uptake into BAT, and caused an increase in whole body energy expenditure.

Source: BMC Pharmacology and Toxicology

DOI: 10.1186/2050-6511-16-s1-a6

Authors: Alexander Pfeifer, Jennifer Etzrodt, Linda S Hoffmann

Institutions: University of Bonn, University Hospital Bonn

Language: English

Topic: Adipose Tissue and Metabolism

Subfield: Physiology (medical)

Field: Medicine

Domain: Health Sciences

SDG: Good health and well-being

Open Access status: gold

Estimated APC paid: $3,090