Metabolically normal obese people are protected from adverse effects following weight gain
Elisa Fabbrini, … , Bruce W. Patterson, Samuel Klein
Elisa Fabbrini, … , Bruce W. Patterson, Samuel Klein
Published January 2, 2015
Citation Information: J Clin Invest. 2015;125(2):787-795. https://doi.org/10.1172/JCI78425.
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Clinical Research and Public Health

Metabolically normal obese people are protected from adverse effects following weight gain

Abstract

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.

Authors

Elisa Fabbrini, Jun Yoshino, Mihoko Yoshino, Faidon Magkos, Courtney Tiemann Luecking, Dmitri Samovski, Gemma Fraterrigo, Adewole L. Okunade, Bruce W. Patterson, Samuel Klein

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Figure 3

Adipose tissue gene expression profile.

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Adipose tissue gene expression profile. PAGE was performed on microarray...
PAGE was performed on microarray data to identify pathways in s.c. adipose tissue that changed with weight gain in MNO (n = 12) and MAO (n = 8) subjects. (A) The top-20 significantly upregulated pathways in MNO subjects are listed on the basis of their Z scores values before and after weight gain. (B) Gene expression of key lipogenic enzymes in s.c. adipose tissue was determined by real-time PCR in MNO and MAO subjects before (white bars) and after (black bars) weight gain. ANCOVA was used for statistical analysis, with the intervention as the within-subjects factor (before vs. after weight gain), the group as the between-subjects factor (MNO vs. MAO), and sex and race as covariates. *P < 0.02, value different from the before–weight-gain value. Data represent the mean ± SEM.