Activation of β₃-adrenoceptors increases in vivo free fatty acid uptake and utilization in brown but not white fat depots in high-fat-fed rats

Abstract

Activation of brown adipose tissue (BAT) and browning of white adipose tissue (WAT) present potential new therapies for obesity and type 2 diabetes. Here, we examined the effects of β-adrenergic stimulation on tissue-specific uptake and storage of free fatty acids (FFA) and its implications for whole body FFA metabolism in diet-induced obese rats using a multi-radiotracer technique. Male Wistar rats were high fat-fed for 12 wk and administered β3-agonist CL316,243 (CL, 1 mg·kg·day) or saline via osmotic minipumps during the last 3 wk. The rats were then fasted and acutely infused with a tracer mixture ([C]palmitate and the partially metabolized R-[H]bromopalmitate) under anesthesia. CL infusion decreased body weight gain and fasting plasma glucose levels. While core body temperature was unaffected, infrared thermography showed an increase in tail heat dissipation following CL infusion. Interestingly, CL markedly increased both FFA storage and utilization in interscapular and perirenal BAT, whereas the flux of FFA to skeletal muscle was decreased. In this rat model of obesity, only sporadic populations of beige adipocytes were detected in the epididymal WAT depot of CL-infused rats, and there was no change in FFA uptake or utilization in WAT following CL infusion. In summary, β-agonism robustly increased FFA flux to BAT coupled with enhanced utilization. Increased BAT activation most likely drove the increased tail heat dissipation to maintain thermostasis. Our results emphasize the quantitative role of brown fat as the functional target of β-agonism in obesity.

The cold-induced lipokine 12,13-diHOME promotes fatty acid transport into brown adipose tissue

“…6d). These results, taken together with well-supported reports that activated BAT takes up large quantities of FA from circulating triglyceride-rich lipoproteins 23–27 , led us to test the effects of 12,13-diHOME on lipid uptake in vivo . Because 12, 13-diHOME decreased circulating triglycerides levels and the principal source of FA in vivo is in the form of triglycerides packaged into lipoproteins, we measured the effect of 12,13-diHOME on the uptake of radiolabeled triglycerides delivered by oral gavage (Fig.…”

Experimental Pharmacological Research Regarding the Effect of Some Newly Synthesized Β-Phenylethyl Amines on the Modified Parameters of the Lipid Metabolism

“…Our analysis u revealed a similar correlation between HDL and oxidative stress. Our study brings new approaches regarding the potential anti-lipidic effects of β 3 agonists and also as possible modulators of lipid peroxidation, results confirmed by other literature data [19,20].…”

“…The involvement of the adrenergic transmission via β 3 receptors in modulating the lipid metabolism was demonstrated in preclinical researches [20]. Studies on obese rodents treated with β 3 adrenergic receptors agonists [18,19] have shown a significant decrease in their body mass and a reduction of adipose tissue without affecting the daily diet ratios.…”

Leptin and brain–adipose crosstalks

“…1a) with the characteristics of brown fat cells (including expression of mitochondrial brown fat uncoupling protein 1 (UCP1), and high mitochondria content) 7 . Development of these brite cells improves insulin sensitivity and systemic metabolism 7 , yet the thermogenic potential of BeAT is still controversial 11,97 .…”