Exploring the emerging complexity in transcriptional regulation of energy homeostasis

Abstract

Obesity and its associated diseases are expected to affect more than 1 billion people by the year 2030. These figures have sparked intensive research into the molecular control of food intake, nutrient distribution, storage and metabolism--processes that are collectively termed energy homeostasis. Recent decades have also seen dramatic developments in our understanding of gene regulation at the signalling, chromatin and post-transcriptional levels. The seemingly exponential growth in this complexity now poses a major challenge for translational researchers in need of simplified but accurate paradigms for clinical use. In this Review, we consider the current understanding of transcriptional control of energy homeostasis, including both transcriptional and epigenetic regulators, and crosstalk between pathways. We also provide insights into emerging developments and challenges in this field.

A compendium of human genes regulating feeding behavior and body weight, its functional characterization and identification of GWAS genes involved in brain-specific PPI network

“…3), and the total number of overrepresented pathways found after analysis (Additional file 2: Figure S1) performed for additional five gene sets ( Publications , OMIM_allelic_variants , OMIM_all_text , Syndromes and GWAS meta-analysis ) was 44. This result is in good agreement with the notion that the process of body weight regulation is very complex [29, 63–65]. Pathway analysis provided evidence that elevated BMI might result from abnormalities in a large number of particular cellular or organismal processes ( signaling molecules and interaction , signal transduction , or development ) and organismal systems ( endocrine or excretory system ).…”

Integrative Transcriptome Analyses of Metabolic Responses in Mice Define Pivotal LncRNA Metabolic Regulators

“…Cellular nutrient sensing involves a myriad of signaling cascades that ultimately convene on a number of key transcription factors to activate or suppress their target metabolic genes (Lempradl et al, 2015). The regulation of lncRNAs by nutrients and hormones suggests that these lncRNAs might be controlled by known master transcription factors of energy metabolism.…”

“…Maintenance of metabolic homeostasis is one of the most fundamental processes required for life, and energy metabolism is intrinsically connected to nearly all essential biological and physiological activities in cells and in whole animals (Lempradl et al, 2015). From a systemic perspective, key metabolic organs in mammals engage in constant dialogues using endocrine factors to regulate overall energy balance.…”

Molecular Pathways: Metabolic Control of Histone Methylation and Gene Expression in Cancer

“…Many chromatin modifying enzymes often require a specific metabolite cofactor to function (12, 13). For example, HMT requires S-adenosylmethionine (SAM), an intermediate metabolite in one-carbon metabolism, to methylate histone (14).…”

“…In cancer cells, metabolic networks are further complicated by oncogenic stimuli, genetic alterations of metabolic enzymes, and the tumor microenvironment, such as hypoxia and nutrient depletion (16). Emerging evidence suggests that changing metabolite levels can regulate enzymatic activity of chromatin modifying proteins, indicating potential crosstalk between cellular metabolism and epigenetics (12, 13). Therefore, besides mutation of epigenetic enzymes, modulation of metabolite levels provides an additional layer of epigenetic control and transcriptional regulation in cancer cells.…”