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Cited by 203Regulation of Appetite and ObesityAdipokines, Inflammation, and Metabolic DiseasesPeroxisome Proliferator-Activated Receptors

Obesity I: Overview and molecular and biochemical mechanisms

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Lustig, Robert H., Collier, David, Kassotis, Christopher, Roepke, Troy A., Kim, Min Ji, Blanc, Etienne, Barouki, Robert, Bansal, Amita +10 more·2022·Biochemical Pharmacology
DOI 10.1016/j.bcp.2022.115012PMC PMC9050949
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Abstract

Obesity is a chronic, relapsing condition characterized by excess body fat. Its prevalence has increased globally since the 1970s, and the number of obese and overweight people is now greater than those underweight. Obesity is a multifactorial condition, and as such, many components contribute to its development and pathogenesis. This is the first of three companion reviews that consider obesity. This review focuses on the genetics, viruses, insulin resistance, inflammation, gut microbiome, and circadian rhythms that promote obesity, along with hormones, growth factors, and organs and tissues that control its development. It shows that the regulation of energy balance (intake vs. expenditure) relies on the interplay of a variety of hormones from adipose tissue, gastrointestinal tract, pancreas, liver, and brain. It details how integrating central neurotransmitters and peripheral metabolic signals (e.g., leptin, insulin, ghrelin, peptide YY 3-36) is essential for controlling energy homeostasis and feeding behavior. It describes the distinct types of adipocytes and how fat cell development is controlled by hormones and growth factors acting via a variety of receptors, including peroxisome proliferator-activated receptor-gamma, retinoid X, insulin, estrogen, androgen, glucocorticoid, thyroid hormone, liver X, constitutive androstane, pregnane X, farnesoid, and aryl hydrocarbon receptors. Finally, it demonstrates that obesity likely has origins in utero. Understanding these biochemical drivers of adiposity and metabolic dysfunction throughout the life cycle lends plausibility and credence to the "obesogen hypothesis" (i.e., the importance of environmental chemicals that disrupt these receptors to promote adiposity or alter metabolism), elucidated more fully in the two companion reviews.

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  • As public health services, food production, and living standards have improved, the definition of malnutrition has become less clear as conditions such as obesity, cachexia, sarcopenia, and micronutrient imbalances have become more prevalent.

    “However, as public health services, food production, and living standards have improved, the definition of malnutrition has become less clear as conditions such as obesity, cachexia, sarcopenia, and micronutrient imbalances have become more prevalent (3–5).”

    From Evolution of the diagnosis of malnutrition in adults: a primer for clinicians (2024) · cites this paper as [3]

    The Introduction and secular trends section (page unavailable) reports that obesity rates have tripled since the 1970s, supporting the claim that obesity has become more prevalent. It does not link that trend to improved public health services, food production, or living standards, or say that the definition of malnutrition has become less clear. The searched passages also do not establish rising prevalence of cachexia, sarcopenia, or micronutrient imbalances. (LLM, conf=0.84)

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Authors
Lustig, R. H., Collier, D., Kassotis, C., Roepke, T. A., Kim, M. J., Blanc, E., Barouki, R., Bansal, A., Cave, M. C., Chatterjee, S., Choudhury, M., Gilbertson, M., Lagadic-Gossmann, D., Howard, S., Lind, L., Tomlinson, C. R., Vondracek, J., & Heindel, J. J.
Affiliations
  • University of California, San Francisco (US)
  • East Carolina University (US)
  • Wayne State University (US)
  • Rutgers, The State University of New Jersey (US)
  • Inserm (FR)
  • Australian National University (AU)
  • University of Louisville (US)
  • University of South Carolina (US)
  • Texas A&M University (US)
  • University of Stirling (GB)
  • Commonweal (US)
  • Uppsala University (SE)
  • Dartmouth College (US)
Corresponding author
Heindel, Jerrold J.
ORCID
Venue
Biochemical Pharmacology
Publisher
Elsevier BV
Published
2022-05
Volume
199
Pages
115012
ISSN
0006-2952 (ISSN-L)
DOI
10.1016/j.bcp.2022.115012
PMC
PMC9050949
OpenAlex
W4223954920
Cited by
203
References
54
Citations by year
2026: 40 · 2025: 54 · 2024: 56 · 2023: 42 · 2022: 11
FWCI
5.87
Type
journal article
Language
en
Open access
Licence
Locations
  • Biochemical Pharmacology (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • HAL (submittedVersion)
Funders
  • National Institute of Mental Health (R01MH123544)
  • National Institute of General Medical Sciences (P20GM103641)
  • National Institute of Diabetes and Digestive and Kidney Diseases (P30DK063720)
  • National Institute of Environmental Health Sciences (R21ES031510, R01ES032189, P01ES028942, R35ES028373, P30ES030283, R00ES030405, P42ES023716, T32ES011564, P30ES005022, P30ES025128)
  • National Center for Complementary and Integrative Health (P01AT003961)
Topics
  • Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
  • Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Peroxisome Proliferator-Activated Receptors
Keywords
obesity, energy balance, energy homeostasis, feeding behavior, leptin, insulin resistance, ghrelin, PYY3-36, adipocytes, adipogenesis, PPARγ, nuclear receptors, endocrine disruptors, gut microbiota, inflammation, growth factors, hormones, obesity pathogenesis
MeSH terms
Adipose Tissue, Energy Metabolism, Humans, Insulin, Obesity, Adipocytes, Leptin

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