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Adipocyte and Cell Biology

Adipose tissue function and insulin sensitivity in syndromic obesity of Bardet-Biedl syndrome

International Journal of Obesity volume 47, pages 382–390 (2023)Cite this article

Subjects

Abstract

Background

Bardet–Biedl syndrome (BBS) is a rare autosomal recessive syndromic obesity of childhood onset among many other features. To date, the excess risk of metabolic complications of severe early-onset obesity in BBS remains controversial. In-depth investigation of adipose tissue structure and function with detailed metabolic phenotype has not been investigated yet.

Objective

To investigate adipose tissue function in BBS.

Design

A prospective cross-sectional study.

Main outcome measure

To determine if there are differences in insulin resistance, metabolic profile, adipose tissue function and gene expression in patients with BBS compared to BMI-matched polygenic obese controls.

Method

9 adults with BBS and 10 controls were recruited from the national centre for BBS, Birmingham, UK. An in-depth study of adipose tissue structure and function along with insulin sensitivity was performed using hyperinsulinemic-euglycemic clamp studies, adipose tissue microdialysis, histology and RNA sequencing, and measurement of circulating adipokines and inflammatory biomarkers.

Results

Adipose tissue structure, gene expression and in vivo functional analysis between BBS and polygenic obesity cohorts were similar. Using hyperinsulinemic-euglycemic clamp and surrogate markers of insulin resistance, we found no significant differences in insulin sensitivity between BBS and obese controls. Furthermore, no significant changes were noted in an array of adipokines, cytokines, pro-inflammatory markers and adipose tissue RNA transcriptomic.

Conclusion

Although childhood-onset extreme obesity is a feature of BBS, detailed studies of insulin sensitivity and adipose tissue structure and function are similar to common polygenic obesity. This study adds to the literature by suggesting that it is the quality and quantity of adiposity not the duration that drives the metabolic phenotype.

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Fig. 1: Metabolic variables measured across a hyperinsulinaemic euglycaemic clamp as markers of Insulin resistance.
Fig. 2: Changes in Glycerol levels measured by microdialysis in subcutaneous adipose tissue.
Fig. 3: Subcutaneous adipose tissue histology.

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Data availability

The datasets generated during and analysed during the current study are available with the corresponding author. We will be happy to share anonymised data on reasonable request.

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Acknowledgements

We acknowledge the support of BBS society. The Research was carried out at the National Institute for Health Research (NIHR)/Welcome Trust Birmingham Clinical Research Facility. The views expressed are those of the authors and not necessarily those of the NHS, the NIHR or the Department of Health. Funds were also obtained from French National Agency of research (ANR, Captor) and French foundation for medical research (FRM) (to KC and PBL).

Author information

Authors and Affiliations

  1. Department of Diabetes, Endocrinology and Metabolism, Queen Elizabeth Hospital Birmingham, Birmingham, UK

    Shanat Baig, Subadra Wanninayake, Yasir S Elhassan, Konstantinos Manolopoulos, Sadaf Ali & Tarekegn Geberhiwot

  2. Department of Nephrology, Queen Elizabeth Hospital Birmingham, Birmingham, UK

    Lukas Foggensteiner

  3. Institute of Metabolism and Systems Research, University of Birmingham, Birmingham, UK

    Yasir S Elhassan, Konstantinos Manolopoulos, Sadaf Ali & Tarekegn Geberhiwot

  4. Sorbonne University, INSERM, NutriOmics research Unit, Assistance-Publique Hôpitaux de Paris, Nutrition department, Pitié-Salpêtrière Hospital, Paris, France

    Pierre Bel Lassen & Karine Clément

  5. Department of Cardiology, Queen Elizabeth Hospital Birmingham, Birmingham, UK

    Richard P Steeds

  6. Institute of Cardiovascular Sciences, University of Birmingham, Birmingham, UK

    Richard P Steeds

  7. Oxford Centre for Diabetes, Endocrinology & Metabolism, NIHR Oxford Biomedical Research Centre, University of Oxford, Oxford, UK

    Jeremy W Tomlinson

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Contributions

TH and RS conceived the study and drafted the study protocol. SB drafted the manuscript. SB and Vishy Veeranna (VV), Inherited Metabolic Disorders Research Charge Nurse, were involved in data collection and running of the study. All authors made contributions to data generation and analysis and writing and reviewing the final manuscript.

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Correspondence to Tarekegn Geberhiwot.

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Baig, S., Wanninayake, S., Foggensteiner, L. et al. Adipose tissue function and insulin sensitivity in syndromic obesity of Bardet-Biedl syndrome. Int J Obes 47, 382–390 (2023). https://doi.org/10.1038/s41366-023-01280-x

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