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Metabolic Diseases

Metabolic diseases — type 2 diabetes, obesity, metabolic syndrome — affect hundreds of millions of people and stem from disruptions of the major energy-regulation pathways. Research here explores metabolic pathways, the organs of metabolism and their interactions, in search of new therapeutic targets.

Adipose tissue and its transcriptional regulation hold a notable place in the work to which Inovarion has contributed. Inovarion has collaborated on the study of the GPS2 coregulator — its role in adipocyte reprogramming and beta-cell insulin secretion[7], in the maladaptive expansion of white adipose tissue via the HIF1A factor and its consequences for insulin resistance, in lipid remodelling (the ABCG1 transporter)[9] and in the inflammatory activation of macrophages (with the SMRT corepressor)[3]. These findings highlight an organ-to-organ communication linking adipose tissue to the pancreas and the liver. Other work addresses the “browning” of adipose tissue and the emergence of beige adipocytes (the role of EGR1 and UCP1)[8] — a mechanism of interest for energy expenditure and the fight against obesity — as well as the epigenetic remodelling that accompanies obesity[2].

Hepatic metabolism forms another set of contributions: the role of the phosphate transporter PiT1/SLC20A1 in insulin signalling, of nuclear receptors and vitamin D in cholestasis and cholangiopathy[5], of Kupffer-cell subpopulations in fatty-acid metabolism[6], and of CD4 T-cell autophagy in liver fibrosis[1]. Placental lipid metabolism (PPAR signalling)[10] and Erdheim-Chester disease, where hypoalphalipoproteinaemia is associated with tissue infiltration, further broaden this picture.

This research mobilises RNA sequencing (RNA-seq), chromatin analysis (ChIP-seq, 4C-seq, CRISPRi), tissue-specific knock-out and high-fat-diet-induced obesity mouse models, human adipocyte lines (hMADS), and even a portable amperometric biosensor developed to monitor lipolysis by measuring glycerol[4] — a point-of-care measurement device that illustrates the instrumental dimension of this work. These results have appeared in Cell Reports, Molecular Cell, Molecular Metabolism, Immunity and Nature Communications.

From the fine regulation of a single gene through to organ physiology, this work illustrates a mechanistic approach to metabolic diseases. Cellular and animal models, transcriptomics, epigenomic analysis: Inovarion brings this set of skills to its partners, end to end.

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Representative publications

  1. Sayegh et al. Defective autophagy in CD4 T cells drives liver fibrosis via type 3 inflammation. Nature Communications, 2025. Record → · PubMed
  2. Barilla et al. Transcriptional and epigenetic control of adipocyte remodeling during obesity. Obesity (Silver Spring), 2021. Record → · PubMed
  3. Huang et al. The corepressors GPS2 and SMRT control enhancer and silencer remodeling via eRNA transcription during inflammatory activation of macrophages. Molecular Cell, 2021. Record → · PubMed
  4. Degrelle et al. DietSee: An on-hand, portable, strip-type biosensor for lipolysis monitoring via real-time amperometric determination of glycerol in blood. Anal Chim Acta, 2021. Record → · PubMed
  5. Gonzalez-Sanchez et al. Cholangiopathy aggravation is caused by VDR ablation and alleviated by VDR-independent vitamin D signaling in ABCB4 knockout mice. Biochim Biophys Acta Mol Basis Dis, 2021. Record → · PubMed
  6. Blériot et al. A subset of Kupffer cells regulates metabolism through the expression of CD36. Immunity, 2021. Record → · PubMed
  7. Drareni et al. Adipocyte Reprogramming by the Transcriptional Coregulator GPS2 Impacts Beta Cell Insulin Secretion. Cell Reports, 2020. Record → · PubMed
  8. Bléher et al. Egr1 loss-of-function promotes beige adipocyte differentiation and activation specifically in inguinal subcutaneous white adipose tissue. Scientific Reports, 2020. Record → · PubMed
  9. Barilla et al. Loss of G protein pathway suppressor 2 in human adipocytes triggers lipid remodeling by upregulating ATP binding cassette subfamily G member 1. Mol Metab, 2020. Record → · PubMed
  10. Liu et al. Mining of combined human placental gene expression data across pregnancy, applied to PPAR signaling pathway. Placenta, 2020. Record → · PubMed