Topics in Transcriptional Control of Lipid Metabolism: from Transcription Factors to Gene-Promoter Polymorphisms

Abstract

The central dogma of biology (DNA>>RNA>>Protein) has remained as an extremely useful scaffold to guide the study of molecular regulation of cellular metabolism. Molecular regulation of cellular metabolism has been pursued from an individual enzyme to a global assessment of protein function at the genomic (DNA), transcriptomic (RNA) and translation (Protein) levels. Details of a key role by inhibitory small RNAs and post-translational processing of cellular proteins on a whole cell/global basis are now just emerging. Below we emphasize the role of transcription factors (TF) in regulation of adipogenesis and lipogenesis. Additionally we have also focused on emerging additional TF that may also have hitherto unrecognized roles in adipogenesis and lipogenesis as compared to our present understanding. It is generally recognized that SNPs in structural genes can affect the final structure/function of a given protein. The implications of SNPs located in the non-transcribed promoter region on transcription have not been examined as extensively at this time. Here we have also summarized some emerging results on promoter SNPs for lipid metabolism and related cellular processes.

Increased Adipocyte Area in Injured Muscle With Aging and Impaired Remodeling in Female Mice

“…Expression of Pparg and Cebpa exhibited an agerelated increase in female mice that was most distinct in the old at Day 7 (for both Pparg and Cebpa) and Day 21 (Pparg only). The abundance and maintenance of Pparg expression at both Days 7 and 21 compared to Cebpa suggests a more prominent role in age-and sex-related differences in adipocyte area consistent with previous publications demonstrating that Cebpa acts through induction of Pparg and was not required to promote adipogenesis (32). Thus, sustained elevations of Pparg in old female mice may be a mechanism for the elevated adipocyte area present in old females after CTX injury.…”

“…promote adipogenesis, Pparg and Cebpa (32) in old age female mice. In addition, young females had increased Ly6C + pro-inflammatory monocytes/macrophages preceding the increased Sca-1 + CD45 − cells compared to young male mice.…”

“…To determine molecular events that may drive the age-and sexrelated differences in adipocyte area during muscle regeneration, expression of adipogenic transcription factors Pparg and Cebpa (32) were measured across sex, age, and time points at baseline and following CTX injury. Expression of Pparg and Cebpa (Figure 7) both increased (p ≤ .005) above baseline at Day 7 for both sexes and all age groups following injury, thereby, mirroring the increased adipocyte area present at Day 7 ( Supplementary Figure S2E and F).…”

IRX3 plays an important role in the pathogenesis of metabolic-associated fatty liver disease by regulating hepatic lipid metabolism

“…Transcriptome- and genome-wide association analyses and epigenetic studies are widely used to reveal the molecular pathological mechanisms of MAFLD. A large number of valuable genes of lipid metabolism have been shown to regulate by several important transcription factors, such as PPARs , FXR , C/EBPs , SREBPs and Zfp423 ( 37 ). The transcription factors associated with the MAFLD, including FXR agonists and PPAR-α/δ agonists, have been studied in late-stage clinical trials to treat NASH ( 38 – 40 ).…”

Effects of pregnancy and feeding level on carcass and meat quality traits of Nellore cows

“…situations (Bergen & Burnett, 2012). Moreover, recent studies have shown the ability of the mature adipocyte to dedifferentiate returning into a proliferative state Fernyhough, Hausman, & Dodson, 2008;Kokta, Dodson, Gertler, & Hill, 2004) resulting in different cell lineages such as myogenesis (Dodson et al, 2010;Kazama, Fujie, Endo, & Kano, 2008;Matsumoto et al, 2008;Wei et al, 2012).…”