Pino 2017 Int J Obes (Lond)
|Pino MF, Divoux A, Simmonds AV, Smith SR, Sparks LM (2017) Investigating the effects of Orexin-A on thermogenesis in human deep neck brown adipose tissue. Int J Obes (Lond) 41:1646-53.
Abstract: Despite successful pre-clinical testing, 85% of early clinical trials for novel drugs fail. Most futilities originate from molecular mechanisms of the drug(s) tested. It is critically important to develop validated human cell-based model systems in which animal-based research can be translated in order to complement the preclinical in vivo findings prior to implementation of a clinical trial. Obesity is associated with reduced circulating levels of Orexin-A (OX-A) in humans. OX-A increases thermogenesis in rodent brown adipose tissue (BAT), yet this phenomenon has not been explored in humans.
We established a cell-based model system of human brown and white adipocytes and tested the effects of OX-A on thermogenesis.
Contrary to published in vivo and in vitro reports in rodents, OX-A treatment alone or in combination with an adrenergic stimulus did not enhance thermogenesis nor its related transcriptional program in a human in vitro model of brown adipocytes nor adipose tissue explants.
Translating preclinical findings in human model systems poses a challenge that must be overcome for the development of effective therapeutic compounds and targets.
Labels: MiParea: Respiration, Pharmacology;toxicology Pathology: Obesity
Organism: Human Tissue;cell: Fat Preparation: Intact cells
Coupling state: LEAK, ROUTINE