Adropin Slightly Modulates Lipolysis, Lipogenesis and Expression of Adipokines but Not Glucose Uptake in Rodent Adipocytes.

Adropin is a peptide hormone which modulates energy homeostasis and metabolism. In animals with diet-induced obesity, adropin attenuates adiposity and improves lipid and glucose homeostasis. Adropin promotes the proliferation of rodent white preadipocytes and suppresses their differentiation into adipocytes. By contrast, the effects of adropin on mature white adipocytes are unknown. Therefore, we aimed to evaluate the effects of adropin on lipolysis, lipogenesis and glucose uptake in white rodent adipocytes. We assessed the effects of adropin on the mRNA expression of adiponectin, resistin and visfatin. White preadipocytes were isolated from male Wistar rats. Differentiated 3T3-L1 cells were used as a surrogate model of white adipocytes. Lipolysis was measured by the evaluation of glycerol and free fatty acid secretion using colorimetric kits. The effects of adropin on lipogenesis and glucose uptake were measured using radioactive-labelled glucose. The expression of adipokine mRNA was studied using real-time PCR. Our results show that adropin slightly promotes lipolysis in rat adipocytes and 3T3-L1 cells. Adropin suppresses lipogenesis in rat adipocytes without influencing glucose uptake. In addition, adropin stimulates adiponectin mRNA expression and suppresses the expression of resistin and visfatin. These results indicate that adropin may be involved in controlling lipid metabolism and adipokine expression in white rodent adipocytes.

The effects of neuronostatin on proliferation and differentiation of rat primary preadipocytes and 3T3-L1 cells.

Neuronostatin is a peptide hormone encoded by the somatostatin gene. Biological effects of neuronostatin are mediated through activation of GPR107. There is evidence indicating that neuronostatin modulates energy homeostasis by suppressing food intake and insulin secretion, while stimulating glucagon secretion. While it was found that neuronostatin receptor is expressed in white adipose tissue, the role of neuronostatin in controlling adipose tissue formation is unknown. The aim of this study is to investigate the effects of neuronostatin on proliferation and differentiation of rat primary preadipocytes and 3T3-L1 cells. We found that neuronostatin receptor GPR107 is expressed in rat preadipocytes and 3T3-L1 cells. Neuronostatin promotes proliferation of preadipocytes via AKT activation. Downregulation of GPR107 mRNA expression and protein production results in an attenuation of neuronostatin-induced stimulation of preadipocyte proliferation. Moreover, neuronostatin reduces intracellular lipid content and the expression of adipogenesis-modulating genes C/ebpα, C/ebpß, Pparγ, and Fabp4. In summary, these results show that neuronostatin, AKT-dependently, stimulates the proliferation of preadipocytes via GPR107. In contrast, neuronostatin inhibits the differentiation of preadipocytes into mature adipocytes.

The Role of Peptide Hormones Discovered in the 21st Century in the Regulation of Adipose Tissue Functions.

Peptide hormones play a prominent role in controlling energy homeostasis and metabolism. They have been implicated in controlling appetite, the function of the gastrointestinal and cardiovascular systems, energy expenditure, and reproduction. Furthermore, there is growing evidence indicating that peptide hormones and their receptors contribute to energy homeostasis regulation by interacting with white and brown adipose tissue. In this article, we review and discuss the literature addressing the role of selected peptide hormones discovered in the 21st century (adropin, apelin, elabela, irisin, kisspeptin, MOTS-c, phoenixin, spexin, and neuropeptides B and W) in controlling white and brown adipogenesis. Furthermore, we elaborate how these hormones control adipose tissue functions in vitro and in vivo.

Adropin stimulates proliferation but suppresses differentiation in rat primary brown preadipocytes.

Adropin is a peptide hormone encoded by Energy Homeostasis Associated (Enho) gene. Adropin modulates glucose and lipid metabolism, and adiposity. Recently, we found that adropin suppresses differentiation of rodent white preadipocytes into mature fat cells. By contrast, the role of adropin in controlling brown adipogenesis is largely unknown. Therefore, in the present study we evaluated the effects of adropin on proliferation and differentiation of adipocyte precursor cells in rats. Brown adipocyte precursor cells were isolated from male Wistar rats. Cell replication was measured by BrdU incorporation. Gene expression was studied using real time PCR. Protein phosphorylation and production was assessed by Western blot. Lipid accumulation was evaluated by Oil Red O staining. Colorimetric kits were used to evaluate glycerol and free fatty acids release. We report here that adropin stimulates proliferation of brown preadipocytes. Moreover, in brown preadipocytes, adropin suppresses mRNA expression of adipogenic genes (C/ebpα, C/ebpß, Pgc1α, Pparγ and Prdm16) during differentiation process. In addition, adropin suppresses UCP1 protein production in brown adipocytes. Finally, adropin reduces intracellular lipid content in brown adipocytes. These results indicate that adropin stimulates proliferation of brown preadipocytes and suppresses their differentiation into mature adipocytes.

Adropin as A Fat-Burning Hormone with Multiple Functions-Review of a Decade of Research.

Adropin is a unique hormone encoded by the energy homeostasis-associated (Enho) gene. Adropin is produced in the liver and brain, and also in peripheral tissues such as in the heart and gastrointestinal tract. Furthermore, adropin is present in the circulatory system. A decade after its discovery, there is evidence that adropin may contribute to body weight regulation, glucose and lipid homeostasis, and cardiovascular system functions. In this review, we summarize and discuss the physiological, metabolic, and pathophysiological factors regulating Enho as well as adropin. Furthermore, we review the literature addressing the role of adropin in adiposity and type 2 diabetes. Finally, we elaborate on the role of adropin in the context of the cardiovascular system, liver diseases, and cancer.

Effects of adropin on proliferation and differentiation of 3T3-L1 cells and rat primary preadipocytes.

Adropin is a protein encoded by Energy Homeostasis Associated (Enho) gene which is expressed mainly in the liver and brain. There is evidence that biological effects of adropin are mediated via GPR19 activation. Animal studies showed that adropin modulates adiposity as well as lipid and glucose homeostasis. Adropin deficient animals have a phenotype closely resembling that of human metabolic syndrome with are obesity dyslipidemia and impaired glucose production. Animals treated with exogenous adropin lose weight, in addition to having reduced expression of lipogenic genes in the liver and fat tissue. While it was shown that adropin may contribute to energy homeostasis and body weight regulation, the role of this protein in controlling fat tissue formation is largely unknown. Thus, in the present study we investigated the effects of adropin on adipogenesis using 3T3-L1 cells and rat primary preadipocytes. We found a low Enho mRNA expression in 3T3-L1 cells and rat primary preadipocytes. Adropin stimulated proliferation of 3T3-L1 cells and rat primary preadipocytes. Stimulation of 3T3-L1 cell proliferation was mediated via ERK1/2 and AKT. Adropin reduced lipid accumulation as well as expression of proadipogenic genes in 3T3-L1 cells and rat preadipocytes, suggesting that this protein attenuates differentiation of preadipocytes into mature fat cells. In summary, these results show that adropin modulates proliferation and differentiation of preadipocytes.

Phoenixin-14 stimulates differentiation of 3T3-L1 preadipocytes via cAMP/Epac-dependent mechanism.

Phoenixin-14 (PNX) is a newly discovered peptide produced by proteolytic cleavage of the small integral membrane protein 20 (Smim20). Previous studies showed that PNX is involved in controlling reproduction, pain, anxiety and memory. Furthermore, in humans, PNX positively correlates with BMI suggesting a potential role of PNX in controlling fat accumulation in obesity. Since the influence of PNX on adipose tissue formation has not been so far demonstrated, we investigated the effects of PNX on proliferation and differentiation of preadipocytes using 3T3-L1 and rat primary preadipocytes. We detected Smim20 and Gpr173 mRNA in 3T3-L1 preadipocytes as well as in rat primary preadipocytes. Furthermore, we found that PNX peptide is produced and secreted from 3T3-L1 and rat primary adipocytes. PNX increased 3T3-L1 preadipocytes proliferation and viability. PNX stimulated the expression of adipogenic genes (Pparγ, C/ebpß and Fabp4) in 3T3-L1 adipocytes. 3T3-L1 preadipocytes differentiated in the presence of PNX had increased lipid content. Stimulation of cell proliferation and differentiation by PNX was also confirmed in rat preadipocytes. PNX failed to induce AKT phosphorylation, however, PNX increased cAMP levels in 3T3-L1 cells. Suppression of Epac signalling attenuated PNX-induced Pparγ expression without affecting cell proliferation. Our data show that PNX stimulates differentiation of 3T3-L1 and rat primary preadipocytes into mature adipocytes via cAMP/Epac-dependent pathway. In conclusion our data shows that phoenixin promotes white adipogenesis, thereby may be involved in controlling body mass regulation.