ArticleEBioMedicine2021
Hyperinsulinemia and insulin resistance in the obese may develop as part of a homeostatic response to elevated free fatty acids: A mechanistic case-control and a population-based cohort study.
Article in EBioMedicine, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT06065930 (Mechanistic Studies in Human Subcutaneous Adipose Tissue), which is not on this map. Cited by 79 papers.
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Mechanistic Studies in Human Subcutaneous Adipose Tissue
Who cites it
79 citing papers in PubMed, 126 citations in OpenAlex.
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- Metabolic dysfunction-associated steatotic liver disease as a systemic disorder: extrahepatic manifestations and the need for data-driven phenotyping.Frontiers in endocrinology · 2026Review
- Effects of a multicomponent intervention on body composition and cardiovascular risk factors in women with obesity- a randomized clinical trial.Journal of diabetes and metabolic disorders · 2025Article
- Cardioprotective Effects of the Natural Antioxidant Epigallocatechin Gallate.Antioxidants (Basel, Switzerland) · 2025Review
- Association and discriminative performance of relative fat mass for frailty index in US older adultsoxy_comment_end.Scientific reports · 2025Article
- Multi-omics analysis reveals the mechanism ofmSystems · 2025Article
- Fishing for a solution: exploring the impact of omega 3 supplement use in childhood obesity.Pediatric research · 2025Article
- Identification of circulating inflammation cytokines as a mediator of gut microbiota and type 2 diabetes mellitus: a Mendelian randomization study.Diabetology & metabolic syndrome · 2025Article
- The flux of energy in critical illness and the obesity paradox.Physiological reviews · 2025Review
- Targeting negative phosphorylation to activate AMPK.Endocrine connections · 2025Article
19 more citing papers are in PubMed but not listed here.
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Authors and funding
13 authors at 5 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundIt is commonly accepted that in obesity free fatty acids (FFA) cause insulin resistance and hyperglycemia, which drives hyperinsulinemia. However, hyperinsulinemia is observed in subjects with normoglycaemia and thus the paradigm above should be reevaluated.
methodsWe describe two studies: MD-Lipolysis, a case control study investigating the mechanisms of obesity-driven insulin resistance by a systemic metabolic analysis, measurements of adipose tissue lipolysis by microdialysis, and adipose tissue genomics; and POEM, a cohort study used for validating differences in circulating metabolites in relation to adiposity and insulin resistance observed in the MD-Lipolysis study.
findingsIn insulin-resistant obese with normal glycaemia from the MD-Lipolysis study, hyperinsulinemia was associated with elevated FFA. Lipolysis, assessed by glycerol release per adipose tissue mass or adipocyte surface, was similar between obese and lean individuals. Adipose tissue from obese subjects showed reduced expression of genes mediating catecholamine-driven lipolysis, lipid storage, and increased expression of genes driving hyperplastic growth. In the POEM study, FFA levels were specifically elevated in obese-overweight subjects with normal fasting glucose and high fasting levels of insulin and C-peptide.
interpretationIn obese subjects with normal glycaemia elevated circulating levels of FFA at fasting are the major metabolic derangement candidate driving fasting hyperinsulinemia. Elevated FFA in obese with normal glycaemia were better explained by increased fat mass rather than by adipose tissue insulin resistance. These results support the idea that hyperinsulinemia and insulin resistance may develop as part of a homeostatic adaptive response to increased adiposity and FFA.
fundingSwedish-Research-Council (2016-02660); Diabetesfonden (DIA2017-250; DIA2018-384; DIA2020-564); Novo-Nordisk-Foundation (NNF17OC0027458; NNF19OC0057174); Cancerfonden (CAN2017/472; 200840PjF); Swedish-ALF-agreement (2018-74560).
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