Intrahepatic lipid, not visceral or muscle fat, is correlated with insulin resistance in older, female rhesus macaques

Authors

  • Michael P. Chu,

    Corresponding author
    1. Department of Medicine, Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland, OR, USA
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  • Bethany J. Klopfenstein,

    1. Department of Medicine, Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland, OR, USA
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  • Christine M. Krisky,

    1. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA
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  • Henryk F. Urbanski,

    1. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA
    2. Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA
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  • William D. Rooney,

    1. Department of Behavioral Neuroscience, Oregon Health and Science University, Portland, OR, USA
    2. Advanced Imaging Research Center, Oregon Health and Science University, Portland, OR, USA
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  • Steven G. Kohama,

    1. Division of Neuroscience, Oregon National Primate Research Center, Oregon Health and Science University, Beaverton, OR, USA
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  • Jonathan Q. Purnell

    1. Department of Medicine, Division of Endocrinology, Diabetes, and Clinical Nutrition, Oregon Health and Science University, Portland, OR, USA
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  • Disclosure: The authors have no competing interests.

  • Author contributions: MC analyzed and interpreted data, performed a literature search, generated figures, and participated in writing of the manuscript. BK conceived the study design, analyzed and interpreted data. CK conceived the study design, collected, analyzed, and interpreted data, generated figures, and participated in writing of the manuscript. HU conceived the study design. WR conceived the study design, collected, analyzed, and interpreted data. SK conceived the study design, collected, analyzed, and interpreted data, and participated in writing of the manuscript. JP conceived the study design, collected, analyzed, and interpreted data, performed a literature search, generated figures, and participated in writing of the manuscript. All authors had final approval of the submitted and published versions of the manuscript.

  • Funding agencies: This publication was made possible with support from the Oregon Clinical and Translational Research Institute (OCTRI), grant number UL1 RR024140 OD-011092 from the National Center for Research Resources (NCRR), a component of the National Institutes of Health (NIH), and NIH Roadmap for Medical Research, NIH grants AG-029612, OD-011092, R03 DK61996 and R01 DK068146 (JQP), as well as Oregon National Primate Research Center (ONPRC) Core grant number 8P51OD011092-53.

Abstract

Objective

Little is known of the effect of body composition on glucose metabolism in the aging female non-human primate. These variables in older female Rhesus macaques were studied.

Design and Methods

Female Rhesus macaques (Macaca mulatta, n = 19, age range 23-30 years) underwent magnetic resonance imaging and 1H spectroscopy to quantify total abdominal fat, visceral fat (VF), subcutaneous fat (SF) area, extramyocellular lipid (EMCL), intramyocellular lipid (IMCL) and intrahepatic lipid (IHL) content, and DEXA scan for whole body composition. A subgroup (n = 12) underwent a fasting blood draw and intravenous glucose tolerance test.

Results

SF correlated with homeostatic model assessment of insulin resistance (HOMAIR) and quantitative insulin sensitivity check index (QUICKI), but not after adjustment for fat mass. IHL demonstrated the strongest correlation with HOMAIR, QUICKI and calculated insulin sensitivity index (CSI), and remained significant after adjustment for fat mass. VF, IMCL, and EMCL did not correlate with any of our measures of insulin sensitivity.

Conclusions

Despite a greater amount of VF compared to SF, VF was not associated with markers of insulin resistance (IR) in the older female monkey. Instead, IHL is a marker for IR in the fasting and post-prandial state in these animals.

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