Metabolic changes in adipose tissues in response to β₃‐adrenergic receptor activation in mice

Abstract

Brown and beige adipocytes dissipate energy as heat. Thus, the activation of brown adipocytes and the emergence of beige adipocytes in white adipose tissue (WAT) are suggested to be useful for preventing and treating obesity. Although β -adrenergic receptor activation is known to stimulate lipolysis and activation of brown and beige adipocytes, fat depot-dependent changes in metabolite concentrations are not fully elucidated. The current study examined the effect of treatment with CL-316,243, a β -adrenergic receptor agonist, on the relative abundance of metabolites in interscapular brown adipose tissue (iBAT), inguinal WAT (ingWAT), and epididymal WAT (epiWAT). Intraperitoneal injection of CL-316,243 (1 mg/kg) for 3 consecutive days increased the relative abundance of several glycolysis-related metabolites in all examined fat depots. The cellular concentrations of metabolites involved in the citric acid cycle and of free amino acids were also increased in epiWAT by CL-316,243. CL-316,243 increased the expression levels of several enzymes and transporters related to glucose metabolism and amino acid catabolism in ingWAT and iBAT but not in epiWAT. CL-316,243 also induced the emergence of more beige adipocytes in ingWAT than in epiWAT. Furthermore, adipocytes surrounded by macrophages were detected in the epiWAT of mice given CL-316,243. The current study reveals the fat depot-dependent modulation of cellular metabolites in CL-316,243-treated mice, presumably resulting from differential regulation of cell metabolism in different cell populations.

Proteomics analysis of adipose depots after intermittent fasting reveals visceral fat preservation mechanisms

“…We observed by untargeted mass spectrometry that the EODF intervention leads to a decreased abundance of ADRB3 protein by 4-fold in vWAT. In scWAT and BAT, ADRB3 protein abundance in mice fed ad libitum was~10-fold less than in vWAT, which agrees with previous mRNA observations (Fujimoto et al, 2019), but the lower abundance prevented consistent quantification by untargeted mass spectrometry. To further elucidate the differences in b-adrenergic receptors between depots, targeted mass spectrometry analysis was performed on ADRB1, ADRB2, and ADRB3.…”

“…Comparing WAT depots, previous data have demonstrated that vWAT is the most catecholamine-sensitive adipose depot (Arner, 2005;Fujimoto et al, 2019;Rebuffé -Scrive et al, 1989). Coupled with the decreased ADRB3 protein abundance after EODF in vWAT, we observed a decrease in fasting-induced phosphorylation of HSL at S660, an essential site for lipolytic activation.…”

Chronic retinoic acid treatment induces differentiation and changes in the metabolite levels of brown (pre)adipocytes

“…Total RNA isolation, cDNA synthesis, and real‐time qRT‐PCR were conducted and quantified, as previously described . The used oligonucleotide primers were previously described . The expression level of the target gene was normalized to the expression level of the TATA‐box binding protein (Tbp).…”

“…Metabolic changes in brown adipocytes activated by ATRA may be distinct from those in brown adipocytes activated by stimulation of β 3adrenergic receptor. Previously, we performed metabolomic analyses in interscapular brown adipose tissue of mice treated with CL-316,243, a β 3 -adrenergic receptor agonist 28 ; contents of some glycolytic metabolites including glucose 6-phosphate and fructose 6phosphate were rather increased in mice treated with CL-316,243, and CL-316,243 did not affect contents of metabolites consisting of citric acid cycle such as fumaric acid and malic acid. Recently, Ucp1independent activation of thermogenesis was identified in beige adipoctytes.…”

“…25 The used oligonucleotide primers were previously described. 18,[26][27][28] The expression level of the target gene was normalized to the expression level of the TATA-box binding protein (Tbp).…”