Resveratrol Inhibits Proliferation and Differentiation of Porcine Preadipocytes by a Novel LincRNA-ROFM/miR-133b/AdipoQ Pathway

Abstract

Resveratrol (RES) has a wide range of biological and pharmacological activities with various health benefits for humans as a food additive. In animal production, RES has been considered a potential functional feed additive for producing high-quality pork. Long noncoding RNAs (lncRNAs) have emerged as essential regulators of fat metabolism, and phytochemicals can regulate fat metabolism through lncRNA. However, it is unclear whether RES can improve back-fat thickness by regulating lncRNA. In this study, we identified a novel lncRNA, which was named a long intergenic non-protein coding RNA, a regulator of fat metabolism (LincRNA-ROFM), from our previous lncRNA sequencing data. LincRNA-ROFM can inhibit adipocyte proliferation and differentiation. In-depth analyses showed that LincRNA-ROFM acts as a molecular sponge for miR-133b, and adiponectin (AdipoQ) is a direct target of miR-133b in porcine preadipocytes. In addition, the expression of LincRNA-ROFM was positively correlated with AdipoQ. RES can promote the expression of LincRNA-ROFM by PPARα and C/EBPα. Altogether, our research showed that LincRNA-ROFM acts as a ceRNA to sequester miR-133b and is upregulated by RES, leading to heightened AdipoQ expression, and thus decreased adipocyte proliferation and differentiation, which reduces back-fat thickness of pigs. Taken together, the RES/LincRNA-ROFM/miR-133b/AdipoQ regulatory network preliminarily explains the mechanism of action of RES in inhibiting fat deposition, which provides new insight into the downstream mechanism of RES inhibition of fat deposits by regulating the lncRNA.

Protein phosphatase 2A modulation and connection with miRNAs and natural products

“…102 Resveratrol inhibits adipocyte proliferation and differentiation by downregulating miR-133b (Table 4). 103…”

“…141 For PP2A-inhibiting natural products, resveratrol upregulates miR-124-3p, 99 miR-17-5p, 118 miR-18a-5p, 122 miR-200c-3p, 127 and miR-383-5p (Figure 4). 147 In comparison, resveratrol downregulates miR-133b, 103 miR-141-3p, 104 miR-142-3p, 108 miR-155-5p, 112 miR-200c-3p, 129 miR-21-5p, 134 miR-34a-5p, 146 and miR-520 h. 148 Retinoic acid upregulates miR-124-3p, 100 miR-142-3p, 109 miR-155-5p, 113,114 miR-15b-3p, 115 miR-191-5p, 124 miR-21-5p, 130 miR-200a-3p, miR-200c-3p, and miR-141-3p, 105 while downregulating miR-222-3p, 136 miR-92a-3p, 149 miR-19a-3p, 125 miR-17-5p, 119 miR-17-5p, 120 and miR-18a-5p. 123 Generally, the same PP2A-modulating natural products may upregulate or downregulate various miRNAs to generate diverse cellular responses by inducing or inhibiting PP2A, as demonstrated across various studies.…”

“…For PP2A‐inhibiting natural products, resveratrol upregulates miR‐124‐3p, 99 miR‐17‐5p, 118 miR‐18a‐5p, 122 miR‐200c‐3p, 127 and miR‐383‐5p (Figure 4). 147 In comparison, resveratrol downregulates miR‐133b, 103 miR‐141‐3p, 104 miR‐142‐3p, 108 miR‐155‐5p, 112 miR‐200c‐3p, 129 miR‐21‐5p, 134 miR‐34a‐5p, 146 and miR‐520 h 148 . Retinoic acid upregulates miR‐124‐3p, 100 miR‐142‐3p, 109 miR‐155‐5p, 113,114 miR‐15b‐3p, 115 miR‐191‐5p, 124 miR‐21‐5p, 130 miR‐200a‐3p, miR‐200c‐3p, and miR‐141‐3p, 105 while downregulating miR‐222‐3p, 136 miR‐92a‐3p, 149 miR‐19a‐3p, 125 miR‐17‐5p, 119 miR‐17‐5p, 120 and miR‐18a‐5p 123 …”