Knockdown of LGALS12 inhibits porcine adipocyte adipogenesis via PKA–Erk1/2 signaling pathway

Abstract

Increasing intramuscular (IM) fat while concomitantly decreasing subcutaneous (SC) fat content is one major goal of pig breeding. Identifying genes involved in lipid metabolism is critical for this goal. Galectin-12 (LGALS12) has been proven to be an important regulator of fat deposition in mouse models; however, the effect and regulatory mechanisms of LGALS12 on porcine adipogenesis are still unknown. In this study, the effects of LGALS12 on fat deposition were explored with primary culture of porcine SC and IM adipocytes. Analysis of LGALS12 expression across different tissues revealed that LGALS12 was predominantly expressed in adipose tissue. The LGALS12 expression patterns across stages of adipocyte differentiation were also evaluated, with differences observed between SC and IM fat. Small interfering RNA (siRNA) of LGALS12 was designed and transfected into porcine adipocytes derived from SC and IM fat. After transfection, the expression level of LGALS12 was significantly reduced, and the number of lipid droplets was reduced in adipocytes from both SC and IM fat. Simultaneously, the levels of adipogenic markers, including PPARγ and aP2, were decreased, whereas hydrolysis markers, including adipose triglyceride lipase (ATGL) and hormone-sensitive lipase (HSL), were increased. Furthermore, the activation of lipolysis signals, such as the phosphorylation of PKA and Erk1/2, were observed with LGALS12 knockdown in terminally differentiated adipocytes from both SC and IM sources. Taken together, these results suggest that LGALS12 knockdown can inhibit adipogenesis of porcine adipocytes by downregulating lipogenic genes and activating the PKA-Erk1/2 signaling pathway.

Comprehensive transcriptomic view of the role of the LGALS12 gene in porcine subcutaneous and intramuscular adipocytes

“…In an earlier study, we demonstrated that a knockdown of LGALS12 could decrease the triglyceride (TG) content and alter the expression of FAS , HSL and ATGL in both IM and SC adipocytes [14]. In inhibitor experiments, the decrease of the TG content (Fig.…”

“…Ablation of this protein in mice leads to increased lipolysis, decreased adiposity, and amelioration of insulin resistance associated with weight gain [10]. Our previous study with porcine adipocytes showed that the knockdown of LGALS12 decreased adipogenesis, which indicates that it has potential value in pig breeding [14]. However, the regulatory mechanisms of LGALS12 in porcine adipocytes remain unclear.…”

The Emerging Role of Galectins and O-GlcNAc Homeostasis in Processes of Cellular Differentiation

“…The similar galectin-12-associated signaling pathways were proposed for differentiation of human sebocytes considering that both the sebaceous gland tissue and sebaceous gland SZ95 cells express same lipogenic factors (C/EBPα, SREBP-1, SCD, and resistin) as adipocytes [ 187 ]. The siRNA knockdown of galectin-12 was also reported to inhibit adipogenesis of porcine adipocytes by downregulating lipogenic genes ( PPARγ and aP2 ) and activating lipid hydrolysis (triglyceride lipase and hormone-sensitive lipase) through the PKA-Erk1/2 signaling pathway [ 188 ]. Lastly, a positive association between cell differentiation (enterocyte lineage) and de novo galectin-12 expression was reported in eight human colorectal carcinoma cell lines (HCT15, KM12, LS180, TC7, CX1, HT-29, SW480, and SW707), which were treated with sodium butyrate [ 189 ].…”

Curcumin represses lipid accumulation through inhibiting ERK1/2-PPAR-γ signaling pathway and triggering apoptosis in porcine subcutaneous preadipocytes

“…In addition, the lipids-lowering effect of CUR has been also proved in obese mice [ 26 ]. In a diabetic rat model, CUR reduces the contents of triglycerides, total cholesterol, blood glucose and free fatty acids [ 27 ]. These related in vivo investigations indirectly and strongly support our results.…”