[Thermoneutrality and animal study]. / Thermoneutralité chez la souris et expérimentation animale.

Animal models remain important for the study of human pathologies. The most widely used model (mouse) is an endothermic mammal like humans, maintained at ambient temperatures (22 °C). Its energy metabolism is overactivated, a situation rarely observed in humans thanks to various adaptations (clothing, heating…). The thermoneutral zone is defined as a range of ambient temperatures that allows an organism to regulate body temperature without using additional thermoregulatory processes. There are many examples of divergent results between studies conducted at 22 °C or at 30 °C (thermoneutrality for mice). Therefore, it seems essential to take into account the housing temperature both for animal welfare and for the relevance of the results.

Title: Thermoneutralité chez la souris et expérimentation animale. Abstract: Les modèles animaux demeurent une nécessité pour l'étude des maladies humaines. Le modèle le plus utilisé, la souris, est, comme les êtres humains, un mammifère endotherme maintenu à des températures ambiantes (22 °C). Son métabolisme énergétique est donc suractivé, une situation rarement observée chez les êtres humains grâce à diverses adaptations (vêtements, chauffage, etc.). La zone de thermoneutralité est définie comme une plage de températures ambiantes qui permet à un organisme de réguler sa température corporelle sans recourir à des processus de thermorégulation supplémentaires. Il existe de nombreux exemples de résultats divergents entre des études menées à 22 °C et celles réalisées à 30 °C (thermoneutralité chez la souris). Il semble donc essentiel de prendre en compte la température d'hébergement tant pour le bien-être animal que pour la pertinence des résultats des expériences réalisées.

Effects of Fatty Acid Metabolites on Adipocytes Britening: Role of Thromboxane A2.

Obesity is a complex disease highly related to diet and lifestyle and is associated with low amount of thermogenic adipocytes. Therapeutics that regulate brown adipocyte recruitment and activity represent interesting strategies to fight overweight and associated comorbidities. Recent studies suggest a role for several fatty acids and their metabolites, called lipokines, in the control of thermogenesis. The purpose of this work was to analyze the role of several lipokines in the control of brown/brite adipocyte formation. We used a validated human adipocyte model, human multipotent adipose-derived stem cell model (hMADS). In the absence of rosiglitazone, hMADS cells differentiate into white adipocytes, but convert into brite adipocytes upon rosiglitazone or prostacyclin 2 (PGI2) treatment. Gene expression was quantified using RT-qPCR and protein levels were assessed by Western blotting. We show here that lipokines such as 12,13-diHOME, 12-HEPE, 15dPGJ2 and 15dPGJ3 were not able to induce browning of white hMADS adipocytes. However, both fatty acid esters of hydroxy fatty acids (FAHFAs), 9-PAHPA and 9-PAHSA potentiated brown key marker UCP1 mRNA levels. Interestingly, CTA2, the stable analog of thromboxane A2 (TXA2), but not its inactive metabolite TXB2, inhibited the rosiglitazone and PGI2-induced browning of hMADS adipocytes. These results pinpoint TXA2 as a lipokine inhibiting brown adipocyte formation that is antagonized by PGI2. Our data open new horizons in the development of potential therapies based on the control of thromboxane A2/prostacyclin balance to combat obesity and associated metabolic disorders.

The Rosmarinus Bioactive Compound Carnosic Acid Is a Novel PPAR Antagonist That Inhibits the Browning of White Adipocytes.

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 ß-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.