
-   ADFP is over-expressed at both mRNA and protein levels in clear-cell RCC. And low-grade clear-cell RCCs have a tendency to express higher ADFP mRNA compared to high-grade tumors. These data strongly suggest that over-expression of ADFP is implicated in lipid uptake and storage in clear-cell RCC. Also, RCCs that express higher levels of ADFP may in part reflect VHL alteration status. VHL tumor suppressor, a key regulator of hypoxia inducible factor (HIF)-alpha, is frequently mutated and inactivated in clear-cell RCC [PMID: 10878807, PMID: 7915601]. ADFP is also a hypoxia inducible gene [PMID: 12387890]. Taken together, the data suggested that upregulation of ADFP expression is due to the disruption of the VHL/HIF pathway [PMID: 15682440].
-   Intestinal microbiota are critical determinants of obesity and metabolic disease risk. When fed a high-fat/low-carbohydrate (HF) diet, the microbiota of Plin2-null mice exhibited the coordinated upregulation of metabolic enzymes directing flux towards the production of growth metabolites such as fatty acids, nucleotides, and amino acids. Plin2 is identified as a specific host determinant of diet effects on microbial function [PMID: 28877764].
-   PPARgamma is abundantly expressed in adipose tissue and colonic epithelium and activation of PPARgamma was reported to attenuate colitis activity and colon cancers [PMID: 12557142, PMID: 12370429]. Adipophilin gene expression can be significantly induced by activation of PPARgamma in human colonic epithelial cells, which coincide with significant decrease in cell proliferation [PMID: 15764152].

## Summary

Plin2, encoded by the PLIN2 gene, produces a protein involved in the formation and maintenance of lipid storage droplets, particularly in adipose tissue but also in various other cell types [CS: 10]. This protein, known as adipophilin or ADFP, is critical in lipid metabolism, particularly in regulating lipid accumulation and the stabilization of lipid droplets [CS: 9]. Its expression is modulated by several factors, including PPARgamma activation, fatty acid levels, and hypoxic conditions [CS: 8].

In the context of the colon, Plin2's dysregulation appears to be linked to conditions of stress or disease [CS: 7]. For instance, the activation of PPARgamma, a nuclear receptor involved in adipogenesis and lipid metabolism, upregulates Plin2 expression [CS: 9]. In diseases like ulcerative colitis, PPARgamma activation increases adipophilin mRNA expression and leads to a decrease in inflammatory markers such as TNF-alpha, IL-1beta, and IL-13 [CS: 6]. This suggests that Plin2 expression, stimulated by PPARgamma, may contribute to a protective or mitigating response against inflammation by aiding in lipid accumulation and regulating lipid metabolism [CS: 7]. In contrast, the disruption of Plin2 expression, as seen in mice with a high-fat diet, alters gut microbial communities and affects metabolic pathways, indicating its role in maintaining gut homeostasis under dietary stress [CS: 6]. Thus, the upregulation of Plin2 in response to various stressors in the colon appears to be a cellular mechanism for managing lipid metabolism and storage, potentially as a means to counteract inflammatory and hypoxic stress [CS: 7].
