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Updated: Dec 15, 2025
Author Spotlight: Unraveling the Molecular Mechanisms of Brown and Beige Adipocyte Regulation
Published on: January 5, 2024
Identification and characterization of adipose surface epitopes
Yasuhiro Onogi1,2, Ahmed Elagamy Mohamed Mahmoud Khalil1,2, Siegfried Ussar1,2,3
1RG Adipocytes and Metabolism, Institute for Diabetes and Obesity, Helmholtz Diabetes Center, Helmholtz Zentrum München, German Research Center for Environmental Health GmbH, 85764 Neuherberg, Germany.
Abstract:
Adipose tissue is a central regulator of metabolism and an important pharmacological target to treat the metabolic consequences of obesity, such as insulin resistance and dyslipidemia. Among the various cellular compartments, the adipocyte cell surface is especially appealing as a drug target as it contains various proteins that when activated or inhibited promote adipocyte health, change its endocrine function and eventually maintain or restore whole-body insulin sensitivity. In addition, cell surface proteins are readily accessible by various drug classes. However, targeting individual cell surface proteins in adipocytes has been difficult due to important functions of these proteins outside adipose tissue, raising various safety concerns. Thus, one of the biggest challenges is the lack of adipose selective surface proteins and/or targeting reagents. Here, we discuss several receptor families with an important function in adipogenesis and mature adipocytes to highlight the complexity at the cell surface and illustrate the problems with identifying adipose selective proteins. We then discuss that, while no unique adipocyte surface protein might exist, how splicing, posttranslational modifications as well as protein/protein interactions can create enormous diversity at the cell surface that vastly expands the space of potentially unique epitopes and how these selective epitopes can be identified and targeted.
Insights
Targeting cell surface proteins in adipose tissue offers a promising strategy for treating metabolic disorders like obesity. Researchers are exploring unique protein epitopes created by modifications to safely target these cells.
Area of Science:
- Metabolic research
- Pharmacology
- Cell biology
Background:
- Adipose tissue regulates metabolism and is a key target for obesity-related conditions like insulin resistance and dyslipidemia.
- Adipocyte cell surface proteins are attractive drug targets due to their accessibility and role in metabolic health.
- Current challenges include a lack of adipose-selective surface proteins and potential off-target effects due to protein functions in other tissues.
Purpose of the Study:
- To highlight the complexity of targeting adipocyte cell surface proteins.
- To discuss receptor families involved in adipogenesis and mature adipocytes.
- To explore strategies for identifying and targeting unique cell surface epitopes in adipocytes.
Main Methods:
- Review of receptor families in adipogenesis and mature adipocytes.
- Discussion of protein diversity through splicing, posttranslational modifications, and protein interactions.
- Exploration of methods for identifying and targeting selective cell surface epitopes.
Main Results:
- Adipocyte cell surface proteins play crucial roles in metabolism and insulin sensitivity.
- Identifying adipose-selective surface proteins is challenging due to shared protein functions.
- Protein diversity through modifications and interactions creates potential unique epitopes.
Conclusions:
- While unique adipocyte surface proteins may not exist, modifications and interactions create diverse, targetable epitopes.
- Strategies focusing on these unique epitopes can overcome challenges in targeting adipocytes.
- This approach holds potential for developing safer and more effective therapies for metabolic diseases.
