Organ Cross-Talk / Tissuekines in the Emanuelli Group

The Emanuelli Group investigates the complex nature of the signalling involved in the endocrine control of metabolic functions, with a special focus on defining the signals and signalling pathways that orchestrate the functions of adipocytes in metabolic homeostasis and disease.

Research focus

Adipose tissue dysfunction, such as triggered by insulin resistance, is one of the main culprits leading to obesity-associated metabolic complications. Recognizing the factors accountable for dysfunctional adipose tissue and those responsible for the beneficial effect of brown/beige fat, holds promise to open novel potential strategies to halt obesity and associated metabolic disorders.

Employing high throughput and unbiased approaches, the main focus of the Emanuelli Group is to examine the molecular mechanisms underlying the endocrine control of metabolic functions. Specifically, the group uses CRISPR-mediated gene editing and manipulation in cells and animals to define the role of newly identified insulin signalling mediators in regulating adipocyte function and to determine the molecular determinants controlling the activity of brown and beige adipocytes.

Main findings

“Distinct signalling properties of insulin receptor substrate (IRS)-1 and IRS-2 in mediating insulin/IGF-1 action”
Published in Cellular Signalling in 2018 this study uses phosphoproteomic analysis to reveal novel elements of the insulin/IGF-1 signalling pathway. The study reveals both common and distinct insulin/IGF-1 signalling events mediated by specific IRS proteins.

“Bidirectional manipulation of gene expression in adipocytes using CRISPRa and siRNA”
Published in Molecular Metabolism in 2017 this study demonstrates that CRISPRa allows multiplex gene induction in pre- and mature adipocytes in vitro and that adipocyte cell fate can be influenced using CRISPRa. It shows how bidirectional control of gene expression is achievable by combining CRISPRa with siRNA mediated knockdown.

“Interplay between FGF21 and insulin action in the liver regulates metabolism”
Published in the Journal of Clinical Investigation in 2014 this study shows how FGF21 corrects hyperglycemia in diabetic mice independently of insulin action in the liver by increasing energy metabolism via activation of brown fat and browning of white fat, but intact liver insulin action is required for FGF21 to control hepatic lipid metabolism.

Staff of the Emanuelli Group

Group leader: Assistant Professor Brice Emanuelli