TOPIC 1

Progression of obesity and related complications: role of gut microbiota?

TOPIC 2

Intestine as a key player in metabolic disorders

TOPIC 3

Adipose tissue Remodeling

TOPIC 4

Systems’ biology and data integration (transversal WP)

TOPIC 5

Translating our fundamental research for the benefit of patients.

  • Define gut microbiota signature in CMD and evaluate the impact of environment (diet and drugs)
  • Demonstrate causality of CMD microbial signature in the development of CMD or its resolution:
    • in human interventions: Metacardis follow-up (development), diet or bariatric surgery (reversal)
    • in mice: gut microbiota transfer experiments (induce CMD or its reversal)

The intestine is a target for changes in external (food, microbiota) and internal (immune system) environment. Gut adaptation has in turn consequences on gut immunity, epithelial cells homeostasis and key organs for energy balance.

  • Understand WAT fibrosis : role of progenitors:
  • Characterize WAT senescence :
    • Evaluate inappropriate turnover of subcellular components (Lysosomal degradation)
    • Examine PG as gut-derived signaling modulators in AT remodeling

We will develop innovative tools for data analysis, physiological status prediction, and visualisation in metabolic diseases. Convergence of techniques include statistical inferences, machine learning, and mechanistic approach using dynamical systems. This WP is  strongly integrated with the other WPs which produce large-scale data.

Two main axes

  1. Develop innovative diagnosis and predictive factors/tools:
  2. Develop novel approaches for therapy with personalized medicine

Latest Publications

Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

November 18, 2020|Comments Off on Imidazole propionate is increased in diabetes and associated with dietary patterns and altered microbial ecology

Nat Commun 11, 5881 (2020). https://doi.org/10.1038/s41467-020-19589-w
Microbiota-host-diet interactions contribute to the development of metabolic diseases. Imidazole propionate is a novel microbially produced metabolite from histidine, which impairs glucose metabolism...

Weight Loss After Sleeve Gastrectomy: Does Type 2 Diabetes Status Impact Weight and Body Composition Trajectories?

November 4, 2020|Comments Off on Weight Loss After Sleeve Gastrectomy: Does Type 2 Diabetes Status Impact Weight and Body Composition Trajectories?

Obes Surg. 2020 Nov 4. doi: 10.1007/s11695-020-05075-1.
Sleeve gastrectomy (SG), the most frequently performed bariatric procedure, induces marked weight-loss, but with high inter-individual variability...

Lysosomal Acid Lipase Drives Adipocyte Cholesterol Homeostasis and Modulates Lipid Storage in Obesity, Independent of Autophagy

November 3, 2020|Comments Off on Lysosomal Acid Lipase Drives Adipocyte Cholesterol Homeostasis and Modulates Lipid Storage in Obesity, Independent of Autophagy

Diabetes. 2020 Nov 2:db200578. doi: 10.2337/db20-0578
Besides cytoplasmic lipase-dependent adipocyte fat mobilization, the metabolic role of lysosomal acid lipase (LAL), highly expressed in adipocytes is unclear.

Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials

November 2, 2020|Comments Off on Efficacy and safety of setmelanotide, an MC4R agonist, in individuals with severe obesity due to LEPR or POMC deficiency: single-arm, open-label, multicentre, phase 3 trials

Lancet Diabetes Endocrinol. 2020 Oct 30:S2213-8587(20)30364-8.
The melanocortin 4 receptor (MC4R), a component of the leptin–melanocortin pathway, plays a part in bodyweight regulation. Severe early-onset obesity can be caused by biallelic variants in genes that affect the MC4R pathway...

Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity

October 30, 2020|Comments Off on Senescence-associated β-galactosidase in subcutaneous adipose tissue associates with altered glycaemic status and truncal fat in severe obesity

Diabetologia. 2020 Oct 30. doi: 10.1007/s00125-020-05307-0.
Altered adipose tissue secretory profile contributes to insulin resistance and type 2 diabetes in obesity. Preclinical studies have identified senescent cells as a cellular source of proinflammatory factors in adipose tissue of obese mice.

Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

October 12, 2020|Comments Off on Novel loci for childhood body mass index and shared heritability with adult cardiometabolic traits

PLoS Genet. 2020 Oct 12;16(10):e1008718. doi: 10.1371/journal.pgen.1008718. eCollection 2020 Oct
The genetic background of childhood body mass index (BMI), and the extent to which the well-known associations of childhood BMI with adult diseases are explained by shared genetic factors, are largely unknown.

Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity

October 10, 2020|Comments Off on Type 2 diabetes is associated with impaired jejunal enteroendocrine GLP-1 cell lineage in human obesity

Int J Obes. 2020 Oct 9. doi: 10.1038/s41366-020-00694-1.
Altered enteroendocrine cell (EEC) function in obesity and type 2 diabetes is not fully understood. Understanding the transcriptional program that controls EEC differentiation is important because some EEC types harbor significant therapeutic potential for type 2 diabetes.

Relative Adipose Tissue Failure in Alström Syndrome Drives Obesity-Induced Insulin Resistance

September 30, 2020|Comments Off on Relative Adipose Tissue Failure in Alström Syndrome Drives Obesity-Induced Insulin Resistance

Diabetes. 2020 Sep 29:db200647. doi: 10.2337/db20-0647.
Obesity is a major risk factor for insulin resistance (IR) and its attendant complications. The pathogenic mechanisms linking them remain poorly understood, partly due to a lack of intermediary monogenic human phenotypes.

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