Metabolically normal obese people are protected from adverse effects following weight gain
Open accessAbstract
BACKGROUND. Obesity is associated with insulin resistance and increased intrahepatic triglyceride (IHTG) content, both of which are key risk factors for diabetes and cardiovascular disease. However, a subset of obese people does not develop these metabolic complications. Here, we tested the hypothesis that people defined by IHTG content and insulin sensitivity as "metabolically normal obese" (MNO), but not those defined as "metabolically abnormal obese" (MAO), are protected from the adverse metabolic effects of weight gain. METHODS. Body composition, multiorgan insulin sensitivity, VLDL apolipoprotein B100 (apoB100) kinetics, and global transcriptional profile in adipose tissue were evaluated before and after moderate (~6%) weight gain in MNO (n = 12) and MAO (n = 8) subjects with a mean BMI of 36 ± 4 kg/m2 who were matched for BMI and fat mass. RESULTS. Although the increase in body weight and fat mass was the same in both groups, hepatic, skeletal muscle, and adipose tissue insulin sensitivity deteriorated, and VLDL apoB100 concentrations and secretion rates increased in MAO, but not MNO, subjects. Moreover, biological pathways and genes associated with adipose tissue lipogenesis increased in MNO, but not MAO, subjects. CONCLUSIONS. These data demonstrate that MNO people are resistant, whereas MAO people are predisposed, to the adverse metabolic effects of moderate weight gain and that increased adipose tissue capacity for lipogenesis might help protect MNO people from weight gain-induced metabolic dysfunction. TRIAL REGISTRATION. ClinicalTrials.gov NCT01184170. FUNDING. This work was supported by NIH grants UL1 RR024992 (Clinical Translational Science Award), DK 56341 (Nutrition and Obesity Research Center), DK 37948 and DK 20579 (Diabetes Center Grant), and UL1 TR000450 (KL2 Award); a Central Society for Clinical and Translational Research Early Career Development Award; and by grants from the Longer Life Foundation and the Kilo Foundation.
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
The citation lists haven’t been fetched yet
References 47 · Cited by 172
- Authors
- Fabbrini, E., Yoshino, J., Yoshino, M., Magkos, F., Tiemann Luecking, C., Samovski, D., Fraterrigo, G., Okunade, A. L., Patterson, B. W., & Klein, S.
- Corresponding author
- Klein, Samuel
- ORCID
- Venue
- Journal of Clinical Investigation
- Published
- 2015-01-02
- Volume
- 125
- Issue
- 2
- Pages
- 787-795
- ISSN
- 0021-9738 (ISSN-L)
- PMC
- PMC4319438
- OpenAlex
- W2073584727
- Semantic Scholar
- edd8298281dc43a9fb59372ab9d166ed5214c5e4
- Cited by
- 172
- References
- 47
- Citations by year
- 2026: 8 · 2025: 11 · 2024: 15 · 2023: 6 · 2022: 8 · 2021: 17 · 2020: 15 · 2019: 16 · 2018: 15 · 2017: 20 · 2016: 27 · 2015: 13 · 2013: 1
- FWCI
- 21.63
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Journal of Clinical Investigation (publishedVersion)
- Europe PMC (PubMed Central) (publishedVersion)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Digital Commons@Becker (Washington University School of Medicine) (submittedVersion)
- Funders
- Longer Life Foundation
- National Institutes of Health (5p60dk020579-35, KL2TR000450, DK20579, DK56341, RR024992, UL1 TR000450)
- National Institute of Diabetes and Digestive and Kidney Diseases (DK37948, DK20579, DK56341, R01DK037948, P60-DK-020579, P30DK056341, P30DK020579, T32DK007120)
- National Center for Research Resources (UL1RR024992)
- National Center for Advancing Translational Sciences (UL1 TR000450)
- Topics
- Health Sciences › Medicine › Endocrinology, Diabetes and Metabolism › Diabetes, Cardiovascular Risks, and Lipoproteins
- Health Sciences › Medicine › Epidemiology › Adipokines, Inflammation, and Metabolic Diseases
- Health Sciences › Medicine › Epidemiology › Liver Disease Diagnosis and Treatment
- Keywords
- weight gain, insulin resistance, insulin sensitivity, intrahepatic triglyceride, adipose tissue lipogenesis, hepatic insulin sensitivity, skeletal muscle insulin sensitivity, adipose tissue gene expression, metabolic protection, obesity
- MeSH terms
- Adipose Tissue, Adult, Female, Humans, Insulin Resistance, Lipoproteins, VLDL, Male, Middle Aged, Obesity, Body Mass Index, Muscle, Skeletal, Adiposity, Lipogenesis, Apolipoprotein B-100
About these checks
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.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
