A Differential Pattern of Batokine Expression in Perivascular Adipose Tissue Depots From Mice

Abstract

Depending on its anatomical placement, perivascular adipose tissue (PVAT) has been found to possess features more (e.g., aortic thoracic) or less (e.g., aortic abdominal) similar to brown/beige adipose tissue in mice, whereas PVAT surrounding the mesenteric arteries and the caudal part of abdominal aorta is similar to white fat. PVAT is thought to influence vascular function through the effects of adipose-secreted molecules on vessels. Brown adipose tissue was recently shown to play differential secretory role via secretion of the so-called batokines but the involvement of differential batokine production in PVAT brown/beige plasticity was unclear. The current study characterizes for the first time the expression of batokines at aortic thoracic PVAT (tPVAT) and aortic abdominal PVAT (aPVAT) in comparison with typical brown and white adipose depots, in basal and thermogenically activated conditions. We found that both PVAT depots increased their expression of genes encoding the batokines bone morphogenetic protein-8b (BMP8B), fibroblast growth factor-21 (FGF21), and kininogen-2 (KNG2) in response to cold, indicating that, under cold-induced thermogenic activation, both thoracic aorta and abdominal aorta would experience intense local exposure to these PVAT-secreted batokines. In contrast, the gene expression levels of growth/differentiation factor-15 and vascular endothelial growth factor-A were induced only in tPVAT. Under short-term high-fat diet-induced thermogenic activation, the thoracic aorta would be specifically exposed to a local increase in PVAT-originating BMP8B, FGF21, and KNG2. Our data support the notion that acquisition of a brown/beige phenotype in PVAT is associated with upregulation of batokines, mainly BMP8B, FGF21, and KNG2, that can differentially target the vascular system.

Angiotensin II type 2 receptor as a novel activator of brown adipose tissue in obesity

“…38 Likewise iBAT, tPVAT can be metabolically induced by cold, adrenergic agonists, or HFD. [39][40][41] In our work, HFD did not modify tPVAT mass or ETC complex protein levels. Intriguingly, C21 treatment in HFD-fed animals increased complexes I, II, IV, and UCP1, which reflects an increased substrate oxidation and a later dedication of the released energy as heat rather than ATP synthesis.…”

“…For instance, the adipose tissue that surrounds the thoracic portion of the aorta, known as tPVAT presents brown adipocytes and participates in the regulation of the vascular function by releasing anticontractile vasoactive substances such as the adipocyte‐derived relaxing factor (ADRF), angiotensin 1–7, or H 2 O 2. 38 Likewise iBAT, tPVAT can be metabolically induced by cold, adrenergic agonists, or HFD 39–41 . In our work, HFD did not modify tPVAT mass or ETC complex protein levels.…”

“…Thus, indirectly, the amelioration of inflammation and oxidative stress could also explain the enhanced function of the BAT, since both processes have proved to alter mitochondrial structure and function. 39,50,51…”

“…Due to the existing negative cross‐regulation between AT1R and AT2R, the administration of C21 could prevent the inflammation and oxidative stress mediated by AT1R overactivation. Thus, indirectly, the amelioration of inflammation and oxidative stress could also explain the enhanced function of the BAT, since both processes have proved to alter mitochondrial structure and function 39,50,51 …”

Effects of dietary methionine restriction on age‐related changes in perivascular and beiging adipose tissues in the mouse

“…Similarly, we expect that other activators of PVAT thermogenesis, including MetR, may likewise be protective against vascular disease. Cellular mechanisms downstream of thermogenic activation of PVAT include increased mitochondrial activity, activated thermogenic genes, secretion of batokines (originally defined as BAT-secreted factors that improve metabolic efficiency [33]), and suppression of immune-related factors, all of which have the capacity to impact vascular disease [34][35][36][37][38]. Mechanisms of MetR in the PVAT phenotype and impact on vascular disease are currently critical areas of study.…”