| dc.description.abstract | Summary
Excess bodyweight are one of the major global health problems in the world today. In recent years, genetics are demonstrated to play an important role in the development of excess bodyweight, which has led to a massive increase in obesity research. However, the identification and understanding of a large number of factors involved in the development of excess bodyweight are still to be elucidated.
Fat is stored in intracellular lipid droplets (LDs), coated with LD associated proteins. The PAT [Perilipin, Adipose differentiation-related protein (ADFP), and Tail interacting protein of 47 kDa (TIP47)] protein family consists of five evolutionary conserved proteins in mammals, which bind to and coat LDs. The PAT proteins are likely to share the same biological functions; regulation of lipolysis, LD movement, LD fusion, and LD stability.
Earlier work in the research group has demonstrated that the majority of the PAT genes are regulated by members of the peroxisomal proliferator-activated receptor (PPAR) family. PPARs are nuclear receptors (NRs) crucial for whole body lipid homeostasis, and all PPAR isoforms heterodimerize with retinoid X receptors (RXRs) upon DNA binding. PPARá is important in fatty acid (FA) oxidation in liver, muscle and heart tissue, as well as mediating the fasting response. PPARâ/ä has important functions in FA oxidation, and energy uncoupling in muscle and adipose tissue, while PPARã is a master regulator of fat storage. Perilipin and S3-12 are regulated by PPARã in adipocytes. ADFP and lipid storage droplet protein 5 (LSDP5) are induced by PPARá in several tissues, and ADFP is induced by PPARâ/ä.
In this study, two mouse muscle cell lines were established, to elucidate transcriptional regulation of PPARá on S3-12 mRNA expression in muscle. By over-expression or activation of PPARá, evidence is provided, to establish S3-12 as a novel target gene for the PPARá/RXR heterodimer in mouse muscle cells. In addition, we demonstrate PPARá to induce LSDP5 and ADFP mRNA in muscle cells. FAs (probably acting as physiological PPAR ligands), were shown to induce S3-12, LSDP5 and ADFP mRNA stronger than a synthetic PPARá activator, indicating another PPAR to be more relevant in muscle cells. Hence, we analyzed the potency of other PPARs in muscle cells, and found that PPARâ/ä induce PAT genes much stronger than PPARá and PPARã. Thus, the presented data indicate S3-12 to be a novel PPARá target gene, but PPARâ/ä to be a more important PPAR in PAT gene regulation in mouse muscle cells. However, future in vivo and vitro studies involving PPARs and PAT genes are required, before any conclusions can be made. | nor |