Developmental Origin of Fat: Tracking Obesity to Its Source
Open accessAbstract
The development of obesity not only depends on the balance between food intake and caloric utilization but also on the balance between white adipose tissue, which is the primary site of energy storage, and brown adipose tissue, which is specialized for energy expenditure. In addition, some sites of white fat storage in the body are more closely linked than others to the metabolic complications of obesity, such as diabetes. In this Review, we consider how the developmental origins of fat contribute to its physiological, cellular, and molecular heterogeneity and explore how these factors may play a role in the growing epidemic of obesity.
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Brown adipocytes are differentiated from white adipocytes because of their high expression of type 2 iodothyronine deiodinase (DIO2), the transcription coregulators PRDM16 and PGC-1α, and the lipolytic regulator Cidea.
“Brown adipocytes are also differentiated from white adipocytes because of their high expression of type 2 iodothyronnine deiodinase (DIO2), the transcription coregulators, PRDM16 and PGC-1α, and the lipolytic regulator, Cidea ([52](#B52), [131](#B131)).”
From Mitochondrial fatty acid oxidation in obesity (2013) · cites this paper as [52]
Adipose tissue is generally considered to arise from multipotent mesenchymal stem cells of mesodermal origin.
“Adipose tissue is generally considered to arise from the multipotent mesenchymal stem cells of mesodermal origin 89.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [89]
Several developmental signaling molecules implicated in the evolution of mesodermal tissue have been shown to impact early stages of brown fat development, including nodal, wingless, members of the FGF, TGF-β and BMP families and others.
“Several developmental signaling molecules implicated in the evolution of mesodermal tissue have been shown to impact early stages of brown fat development. These include nodal, wingless, members of the fibroblast growth factor (FGF), transforming growth factor-β (TGF-β) and bone morphogenetic protein (BMPs) families and others 89.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [89]
Brown fat differentiation involves mechanisms common to both brown and white adipocyte differentiation, as well as some specific factors.
“At the molecular level, brown fat differentiation involves mechanisms common to both brown and white adipocyte differentiation, as well as some specific factors 89,165–167.”
From Cellular bioenergetics as a target for obesity therapy (2010) · cites this paper as [89]
BAT is especially abundant in hibernating mammals, but can also be found in adult humans.
“BAT is especially abundant in hibernating mammals 74 , but can also be found in adult humans 75.”
From Inter‐organ communication: a gatekeeper for metabolic health (2019) · cites this paper as [74]
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“Obesity develops when energy intake exceeds energy expenditure (1) and is principally characterized by excess adipose tissue (2,3).”
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“In mammals, adipose tissue is composed of white adipose tissue (WAT) and brown adipose tissue (BAT), and their dysfunction can lead to overweight and obesity [2].”
Background
- Authors
- Gesta, S., Tseng, Y.-H., & Kahn, C. R.
- Affiliations
- Joslin Diabetes Center (US)
- Corresponding author
- Kahn, C. Ronald
- Venue
- Cell
- Publisher
- Elsevier BV
- Published
- 2007-10
- Volume
- 131
- Issue
- 2
- Pages
- 242-256
- ISSN
- 0092-8674 (ISSN-L)
- OpenAlex
- W2123371309
- Cited by
- 1,508
- References
- 103
- Citations by year
- 2026: 38 · 2025: 31 · 2024: 72 · 2023: 70 · 2022: 75 · 2021: 100 · 2020: 85 · 2019: 96 · 2018: 80 · 2017: 94 · 2016: 92 · 2015: 103 · 2014: 112 · 2013: 116 · 2012: 97
- FWCI
- 6.19
- Type
- journal article
- Language
- en
- Update notices
- erratum (2008-10-17)
- Open access
- bronze
- doi.org
- Licence
- www.elsevier.com/tdm/userlicense/1.0/ (tdm)
- www.elsevier.com/legal/tdmrep-license (tdm)
- www.elsevier.com/open-access/userlicense/1.0/ (vor, 2152 d)
- doi.org/10.15223/policy-017 (stm-asf)
- doi.org/10.15223/policy-037 (stm-asf)
- doi.org/10.15223/policy-012 (stm-asf)
- doi.org/10.15223/policy-029 (stm-asf)
- doi.org/10.15223/policy-004 (stm-asf)
- Locations
- Cell (publishedVersion)
- PubMed (publishedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases
- Topics
- Health Sciences › Medicine › Physiology › Adipose Tissue and Metabolism
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Birth, Development, and Health
- Keywords
- obesity, white adipose tissue, brown adipose tissue, energy storage, energy expenditure, adipose tissue heterogeneity, diabetes mellitus, adipose tissue development
- MeSH terms
- Animals, Adipose Tissue, Brown, Cell Differentiation, Dietary Fats, Eating, Energy Metabolism, Humans, Obesity, Signal Transduction, Adipocytes, Cell Lineage, Adipose Tissue, White
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Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
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