Abstract
Thermogenic brown and brite adipocytes convert chemical energy from nutrients into heat. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to control fat mass such as in obesity or cachexia. The peroxisome proliferator-activated receptor (PPAR) family plays key roles in the maintenance of adipose tissue and in the regulation of thermogenic activity. Activation of these receptors induce browning of white adipocyte. The purpose of this work was to characterize the role of carnosic acid (CA), a compound used in traditional medicine, in the control of brown/brite adipocyte formation and function. We used human multipotent adipose-derived stem (hMADS) cells differentiated into white or brite adipocytes. The expression of key marker genes was determined using RT-qPCR and western blotting. We show here that CA inhibits the browning of white adipocytes and favors decreased gene expression of thermogenic markers. CA treatment does not affect β-adrenergic response. Importantly, the effects of CA are fully reversible. We used transactivation assays to show that CA has a PPARα/γ antagonistic action. Our data pinpoint CA as a drug able to control PPAR activity through an antagonistic effect. These observations shed some light on the development of natural PPAR antagonists and their potential effects on thermogenic response.
Highlights
Mammalian adipose organs can be divided into two distinct types of adipose tissues: white and brown
Cells have previously been described [28,29]. These cells, which were isolated from white adipose tissue removed from surgical scraps of infants undergoing surgery, did not enter senescence while exhibiting a diploid karyotype, were non-transformed though they expressed significant telomerase activity, did not show any chromosomal abnormalities after 140 population doublings (PDs), and maintained their differentiation properties after 160–200 PDs. human multipotent adipose-derived stem (hMADS) cells were able to withstand freeze/thaw procedures, and their differentiation could be directed under different culture conditions into various lineages [29]
In the first series of experiments, we investigated the effect of carnosic acid (CA) on adipogenesis using a well-characterized human cell model [28]
Summary
Mammalian adipose organs can be divided into two distinct types of adipose tissues: white and brown. White adipose tissue (WAT) is specialized in the storage and release of fatty acids [1], which are required as an energy source for heart and muscles. Brown adipose tissue (BAT) dissipates energy in the form of heat by uncoupling the mitochondrial respiratory chain from ATP synthesis [2,3]. Adipose tissue is the largest endocrine organ and links metabolism and immunity [4]. It is a major actor in the regulation of energetic metabolism and represents a potential therapeutic target to combat fat mass disorders such as obesity and hypermetabolism in critical illness. Various lifestyle interventions and proposed pharmacological remedies have not yet been shown to induce sustained body weight reduction with long-term benefits to the health and well-being of patients with obesity [7]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Free) 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call
