Gluttony, sloth and the metabolic syndrome: a roadmap to lipotoxicity
Open accessAbstract
Once considered divine retribution for sins, comorbidities of obesity (metabolic syndrome) are today attributed to obesity-induced metabolic defects. Here, we propose that obesity and hyperleptinemia protect lipid-intolerant nonadipose organs against lipotoxic lipid spillover during sustained caloric surplus. Metabolic syndrome is ascribed to lipotoxicity caused by age-related resistance to antilipotoxic protection by leptin.
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Not all adipose tissue expansion is necessarily associated with pathological changes.
“However, not all AT expansion is necessarily associated with pathological changes.”
From Adipose tissue remodeling and obesity (2011) · cites this paper as [3]
Excessive renal sinus fat and perirenal fat may also cause lipotoxicity owing to the accumulation of intracellular triglycerides and toxic metabolites such as ceramides.
“Excessive RSF and PRF may also cause lipotoxicity owing to the accumulation of intracellular triglycerides and toxic metabolites such as ceramides57,58.”
From Obesity, kidney dysfunction and hypertension: mechanistic links (2019) · cites this paper as [58]
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Adipokines, Metabolic Syndrome and Rheumatic Diseases
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Adipose Tissue Inflammation in the Pathogenesis of Type 2 Diabetes
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Association of metabolic syndrome and chronic kidney disease
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Deciphering the Role of Lipid Droplets in Cardiovascular Disease
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Brown adipose tissue derived VEGF-A modulates cold tolerance and energy expenditure
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Self-citationRole of Epicardial Adipose Tissue in Health and Disease: A Matter of Fat?
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Tissue-Autonomous Function of Drosophila Seipin in Preventing Ectopic Lipid Droplet Formation
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Lipid Droplet Biogenesis and Function in the Endothelium
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Role of Fat Body Lipogenesis in Protection against the Effects of Caloric Overload in Drosophila
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Innate immune activation in obesity
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Targeting the glucagon receptor family for diabetes and obesity therapy
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Pancreatic Steatosis and Its Relationship to β-Cell Dysfunction in Humans
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“Energy intake reflects mostly the uptake of calorically dense foods, while the energy expenditure side reflects the energy required to meet basic energy demands, energy required for physical activity, and energy expended on adaptive thermogenesis (3,4).”
Self-citationLipid metabolism in sarcopenia
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Organelle biogenesis in the endoplasmic reticulum
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Contribution of Cardiorespiratory Fitness to the Obesity Paradox
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Parturition dysfunction in obesity: time to target the pathobiology
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Loss of the RNA polymerase III repressor MAF1 confers obesity resistancePreprint
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Maternal Obesity Promotes a Proinflammatory Signature in Rat Uterus and Blastocyst
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Drosophila gains traction as a repurposed tool to investigate metabolism
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Macrophages and the Regulation of Adipose Tissue Remodeling
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Health Consequences of Obesity
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SGLT2 inhibitors: their potential reduction in blood pressure
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Insulin resistance protects the heart from fuel overload in dysregulated metabolic states
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- Authors
- Unger, R. H., & Scherer, P. E.
- Affiliations
- Veterans Health Administration (US)
- The University of Texas Southwestern Medical Center (US)
- Corresponding author
- Unger, Roger H.
- ORCID
- Scherer, Philipp E.
- Venue
- Trends in Endocrinology & Metabolism
- Publisher
- Elsevier BV
- Published
- 2010-06
- Volume
- 21
- Issue
- 6
- Pages
- 345-352
- ISSN
- 1043-2760 (ISSN-L)
- PMC
- PMC2880185
- OpenAlex
- W1994949025
- Cited by
- 436
- References
- 53
- Citations by year
- 2026: 20 · 2025: 17 · 2024: 30 · 2023: 18 · 2022: 17 · 2021: 15 · 2020: 21 · 2019: 28 · 2018: 18 · 2017: 24 · 2016: 28 · 2015: 31 · 2014: 50 · 2013: 30 · 2012: 40
- FWCI
- 4.30
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Trends in Endocrinology and Metabolism (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute of Diabetes and Digestive and Kidney Diseases (R01DK002700)
- Topics
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Life Sciences › Neuroscience › Endocrine and Autonomic Systems › Regulation of Appetite and Obesity
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Keywords
- metabolic syndrome, lipotoxicity, obesity, leptin resistance, hyperleptinemia, gluttony, sloths
- MeSH terms
- Adipose Tissue, Energy Intake, Humans, Hyperphagia, Lipids, Obesity, Leptin, Metabolic Syndrome
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