Skip to main content
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care
  • Subscribe
  • Log in
  • My Cart
  • Follow ada on Twitter
  • RSS
  • Visit ada on Facebook
Diabetes

Advanced Search

Main menu

  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
  • More from ADA
    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • ADA Standards of Medical Care in Diabetes
    • ADA Scientific Sessions Abstracts
    • BMJ Open Diabetes Research & Care

User menu

  • Subscribe
  • Log in
  • My Cart

Search

  • Advanced search
Diabetes
  • Home
  • Current
    • Current Issue
    • Online Ahead of Print
    • ADA Scientific Sessions Abstracts
  • Browse
    • By Topic
    • Issue Archive
    • Saved Searches
    • ADA Scientific Sessions Abstracts
    • Diabetes COVID-19 Article Collection
    • Diabetes Symposium 2020
  • Info
    • About the Journal
    • About the Editors
    • ADA Journal Policies
    • Instructions for Authors
    • Guidance for Reviewers
  • Reprints/Reuse
  • Advertising
  • Subscriptions
    • Individual Subscriptions
    • Institutional Subscriptions and Site Licenses
    • Access Institutional Usage Reports
    • Purchase Single Issues
  • Alerts
    • E­mail Alerts
    • RSS Feeds
  • Podcasts
    • Diabetes Core Update
    • Special Podcast Series: Therapeutic Inertia
    • Special Podcast Series: Influenza Podcasts
    • Special Podcast Series: SGLT2 Inhibitors
    • Special Podcast Series: COVID-19
  • Submit
    • Submit a Manuscript
    • Submit Cover Art
    • ADA Journal Policies
    • Instructions for Authors
    • ADA Peer Review
Obesity Studies

Effect of Weight Loss on Insulin Sensitivity and Intramuscular Long-Chain Fatty Acyl-CoAs in Morbidly Obese Subjects

  1. Joseph A. Houmard1,
  2. Charles J. Tanner1,
  3. Chunli Yu2,
  4. Paul G. Cunningham1,
  5. Walter J. Pories1,
  6. Kenneth G. MacDonald1 and
  7. Gerald I. Shulman2
  1. 1Departments of Exercise and Sport Science, Surgery, and the Human Performance Laboratory and Diabetes/Obesity Center, East Carolina University, Greenville, North Carolina
  2. 2Howard Hughes Medical Institute and the Departments of Internal Medicine and Cellular and Molecular Physiology, Yale University School of Medicine, New Haven, Connecticut
    Diabetes 2002 Oct; 51(10): 2959-2963. https://doi.org/10.2337/diabetes.51.10.2959
    PreviousNext
    • Article
    • Figures & Tables
    • Info & Metrics
    • PDF
    Loading

    Abstract

    Increases in intramyocellular long-chain fatty acyl-CoAs (LCACoA) have been implicated in the pathogenesis of insulin resistance in skeletal muscle. To test this hypothesis, we measured muscle (vastus lateralis) LCACoA content and insulin action in morbidly obese patients (n = 11) before and after weight loss (gastric bypass surgery). The intervention produced significant weight loss (142.3 ± 6.8 vs. 79.6 ± 4.1 kg for before versus after surgery, respectively). Fasting insulin decreased by ∼ 84% (23.3 ± 3.8 vs. 3.8 ± 0.5 mU/ml), and insulin sensitivity, as determined by minimal model, increased by ∼360% (1.2 ± 0.3 vs. 4.1 ± 0.5 min−1 · [μ U/kg−1]) indicating enhanced insulin action. Muscle palmityl CoA (16:0; 0.54 ± 0.08 vs. 0.35 ± 0.04 nmol/g wet wt) concentration decreased by ∼35% (P < 0.05) with weight loss, whereas stearate CoA (18:0; −17%; 0.65 ± 0.05 vs. 0.54 ± 0.03 nmol/g wet wt) and linoleate CoA (18:2; −30%; 2.47 ± 0.27 vs. 1.66 ± 0.19 nmol/g wet wt) were also reduced (P < 0.05). There were no statistically significant declines in muscle palmitoleate CoA (16:1), oleate CoA (18:1), or total LCACoA content. These data suggest that a reduction in intramuscular LCACoA content may be responsible, at least in part, for the enhanced insulin action observed with weight loss in obese individuals.

    Recent studies in rodents and humans have demonstrated a strong relationship between insulin resistance in skeletal muscle and increased intramuscular triglyceride (1–4) and intramyocellular triglyceride content, assessed by 1H nuclear magnetic resonance (5–7). Because triglyceride is a relatively inert intracellular metabolite, it is likely that it serves more as a marker for other fatty acid-derived metabolites that actually mediate the insulin resistance, such as cytosolic long-chain acyl-CoA (LCACoA). Cytosolic LCACoA esters are intermediates in lipid synthesis/oxidation and are primarily derived from circulating fatty acids or intramuscular lipid sources such as triglyceride and phospholipid. There is accumulating evidence that LCACoAs are involved in controlling a variety of important cellular functions, including cellular metabolism, signal transduction, and gene expression (8–10). In relation to insulin action, rodents that were fed a high-fat diet had increased intramuscular LCACoA content that was associated with insulin resistance (11). Furthermore, mice with tissue-specific overexpression of lipoprotein lipase in muscle and liver have increased concentrations of LCACoA in these tissues, which is associated with tissue-specific insulin resistance (3). Such observations have led to the hypothesis that LCACoA concentration is an important factor in the pathogenesis of insulin resistance. In support of a role for LCACoA in insulin resistance, a negative correlation between insulin action and total LCACoA content has been reported in human skeletal muscle (11). However, to our knowledge, there is no additional evidence to support the hypothesis that LCACoA concentration is involved in the regulation of insulin action in human skeletal muscle. The purpose of the current study was to use a prospective design to test more rigorously the hypothesis that LCACoA is associated with insulin action in human skeletal muscle. This was accomplished by discerning whether LCACoA content decreased in concert with an intervention, weight loss, known to enhance insulin action (12). In addition, total LCACoA content may not reflect individual alterations in LCACoAs of different chain lengths and/or degrees of saturation; there is also evidence that individual LCACoA species serve different regulatory roles (9,10,13,14). We therefore also measured the concentrations of prevalent acyl-CoA species before and after weight loss.

    RESEARCH DESIGN AND METHODS

    Design and subjects.

    Morbidly obese (BMI >40 kg/m2 and/or at least 100 lb over ideal body weight) subjects (10 women, 2 men; 1 black, 11 white) were examined before and 1 year after elective gastric bypass surgery to induce weight loss (12). Descriptive data for the subjects are presented in Table 1. We have previously characterized responses to gastric surgery in morbidly obese subjects; the 12-month postsurgery time was selected as body mass stabilizes and remains significantly depressed compared with the presurgery condition; there is also a dramatic improvement in insulin action (12). One subject was diabetic (type 2); all others had normal fasting glucose concentrations.

    Subjects reported to the laboratory at ∼0800 h after a 12-h fast. For the 3 days before the study, subjects were instructed to consume at least 250 g of carbohydrate per day. Body mass and stature were measured upon entering the laboratory. A muscle sample was obtained from the vastus lateralis in the fasted state using the needle biopsy technique. A minimal model (15) was then performed for calculating an insulin sensitivity index (SI). Identical procedures were performed when subjects were morbidly obese (before surgery) and after weight loss (1 year after surgery). All procedures were approved by the East Carolina University Institutional Review Board, and informed consent was obtained before any experimental procedures were performed.

    Insulin action.

    Insulin action was determined with a 3-h intravenous glucose tolerance test (minimal model) (15). Glucose and insulin dosages were calculated on the basis of body surface area, because of the high body mass of morbidly obese subjects (R.N. Bergman, personal communication). After fasting samples were obtained, glucose (50%) was injected into a catheter placed in an antecubital vein at a dose of 12 g/m2 body surface area. Insulin, at a dose of 1.5 units/m2 body surface area, was injected at minute 19. Blood samples were obtained at minutes 2, 3, 4, 5, 6, 8, 10, 12, 14, 16, 19, 22, 25, 30, 40, 50, 60, 70, 80, 90, 100, 120, 140, and 160 and centrifuged, and plasma was frozen at −80°C for the subsequent determination of insulin and glucose. Insulin was determined with immunoassay (Access Immunoassay System; Beckman Coulter, Fullerton, CA), and glucose was determined with an oxidation reaction (YSI Model 2300 Stat Plus; Yellow Springs Instruments, Yellow Springs, OH). An insulin SI was calculated on the basis of the minimal model as described by Bergman et al. (15). SI is an index of the ability of insulin to promote the disposal of glucose, with a higher SI indicating enhanced insulin sensitivity. Insulin action was also determined from fasting glucose and insulin concentrations by calculating a homeostasis model assessment (HOMA) value ([fasting glucose (mg/dl) × 0.05551] × fasting insulin [μU/ml]/22.1) (16).

    Liquid chromatography tandem mass spectrometry.

    A needle biopsy of the vastus lateralis was obtained under local anesthesia in the fasted condition, immediately before the minimal model. Visible fat and/or connective tissue was removed from the sample (50–100 mg) and frozen in liquid nitrogen for subsequent analyses. LCACoAs were extracted from the biopsy sample by solid-phase extraction and C17 CoA was added as an internal standard as previously described (17,18). A tandem mass spectrometer API 3000 (Perkin-Elmer Sciex) interfaced with TurboIonspray ionization source was used for mass spectrometry/mass spectrometry analysis (18). Fatty acyl-CoAs were ionized in a negative electrospray mode, and the transition pairs [M-2H]2−/[M-H-80]− were monitored in multiple reaction monitoring mode. Doubly charged ions and corresponding product ions (precursor minus phosphate group) were chosen as a transition pair for multiple reactions monitoring for quantitation (18). Total LCACoA content was calculated as the sum of the LCACoA species measured.

    Statistics.

    Data are presented as mean ± SE. Repeated measures ANOVA was used to compare data before and after surgery. Pearson product correlation coefficients were used to determine whether relationships existed between selected variables. Statistical significance was denoted at P < 0.05.

    RESULTS

    Weight loss.

    The gastric bypass surgery induced substantial weight loss in the morbidly obese subjects. As presented in Fig. 1, body mass decreased significantly (P < 0.0001) by ∼60 kg (142.3 ± 6.8 vs. 79.6 ± 4.1 kg). BMI also decreased (48.6 ± 1.2 vs. 27.1 ± 0.9 kg/m2) significantly (P < 0.0001).

    Insulin action.

    Insulin action, as determined by a variety of indexes, improved with weight loss. As presented in Fig. 2, fasting glucose concentration decreased (P < 0.01) by ∼24% with weight loss (104.3 ± 7.7 vs. 79.6 ± 1.6 mg/dl). Fasting insulin was also reduced (23.3 ± 3.8 vs. 3.8 ± 0.5 μU/ml; P < 0.001) by ∼84% for before versus after weight loss, respectively. Because both glucose and insulin decreased, there was a reduction (P < 0.001) in HOMA (5.9 ± 0.9 vs. 0.8 ± 0.1) with weight loss. SI as determined from the minimal model (15) increased (P < 0.0001) by ∼360% with weight loss, indicating enhanced insulin sensitivity [1.2 ± 0.3 vs. 4.1 ± 0.5 min−1 · (μU/kg−1); Fig. 2]. An SI was not calculated for one female subject because of an inability to obtain venous access during the entire minimal model procedure; SI data are thus presented for 11 subjects. Improvements in these indexes of insulin action remained statistically significant when the diabetic subject was excluded; data from this subject was thus included in all statistical analyses.

    Muscle LCACoA content.

    Data for LCACoA concentrations are presented in Fig. 3. Sufficient material was not obtained in 1 individual; data are presented for 11 subjects (9 women, 2 men). There was no evidence for sex differences in relation to insulin action, body composition, and changes in the total and individual LCACoA species with weight loss intervention. All data are thus presented irrespective of sex. There was a significant (P < 0.05) decline in muscle palmityl CoA (16:0) concentration with weight loss (0.54 ± 0.08 vs. 0.35 ± 0.04 nmol/g wet wt) of ∼35%. Muscle palmitoleate CoA (16:1) did not change (P = 0.23) with weight loss (0.36 ± 0.08 vs. 0.27 ± 0.04 nmol/g wet wt). In terms of 18 carbon fatty acids, muscle stearate CoA (18:0) decreased (P < 0.05) with weight loss (0.65 ± 0.05 vs. 0.54 ± 0.03 nmol/g wet wt) by ∼17%. Muscle oleate CoA (18:1) was not altered (P = 0.25) with weight loss (5.31 ± 0.64 vs. 4.50 ± 0.35 nmol/g wet wt). Linoleate CoA (18:2) was also reduced (P < 0.05) with weight loss (2.47 ± 0.27 vs. 1.66 ± 0.19 nmol/g wet wt) by ∼30%. The relative percentages of total LCACoA content (mean of before and after weight loss) were palmityl CoA 5.2%, palmitoleate CoA 3.6%, stearate CoA 7.2%, linoleate CoA 23.4%, and oleate CoA 60.8%. There was a trend (P = 0.09) for total LCACoA concentration to decrease by ∼20% with weight loss (9.54 ± 1.03 vs. 7.60 ± 0.69 nmol/g wet wt). There was a trend (r = −0.58, P = 0.08) for a greater increase in insulin sensitivity (SI) to be associated with a larger decline in palmityl CoA (16:0) with weight loss. No other correlations between changes in LCACoAs with changes in insulin action and body mass were evident.

    DISCUSSION

    The main finding of the present study was that skeletal muscle LCACoA content decreased in conjunction with enhanced insulin action in obese patients after weight loss. This observation is relevant to discerning mechanisms by which weight loss enhances insulin action, as the accumulation of LCACoA esters induces cellular alterations associated with insulin resistance. LCACoA esters can lead to activation of protein kinase Cθ, which can subsequently activate a serine kinase cascade that phosphorylates the insulin receptor (19) and/or insulin receptor substrate-1 at serine sites (20,21). Serine phosphorylation of the insulin receptor and insulin receptor substrate-1 reduces the ability of the cell to respond to ligand binding and produces insulin resistance (19–24). An intervention that decreases intramuscular LCACoA concentrations thus would be hypothesized to improve insulin action via enhancing insulin signal transduction. LCACoA esters also serve as regulatory molecules that control the activity of key enzymes in glucose metabolism, such as glycogen synthase (8–10,25), hexokinase (26), and nuclear factors that regulate gene transcription (8–10,14). These findings indicate the potential importance of LCACoA and suggest that a reduction in muscle LCACoA concentrations would contribute, at least in part, to enhancing insulin action; the current data support this hypothesis. The novel aspect of the present study was that a reduction in LCACoA was specifically observed in human skeletal muscle with a clinical intervention (weight loss) used to enhance insulin action (Figs. 2 and 3).

    As presented in Fig. 3, palmityl CoA, stearate CoA, and linoleate CoA decreased significantly with weight loss, whereas there was no statistically significant reductions in muscle palmitoleate CoA or oleate CoA. It is of particular interest that both saturated fatty acyl CoAs (palmityl CoA and stearate CoA) decreased significantly with weight loss. Stein et al. (13) reported that saturated fatty acids (palmitic, stearic) promoted the hypersecretion of insulin more dramatically than unsaturated fatty acids of similar chain lengths (linoleic, oleic). These findings prompted the speculation that saturated fatty acids and their derivatives contribute to the development of insulin resistance (13). In support, the consumption of saturated fats is significantly associated with hyperinsulinemia and subsequent disease states such as diabetes, hypertension, and obesity (27). Such data suggest that saturated fatty acids and their metabolic products are relatively potent in terms of functioning as intracellular signaling molecules that induce insulin resistance. Although we cannot discern cause and effect, in the present study we did observe a tendency for a larger reduction in palmityl CoA in human skeletal muscle to be associated with a greater improvement in insulin action with weight loss (results). Palmityl CoA can be synthesized into ceramide (1) and/or possibly function through other mechanisms that induce insulin resistance (22). These findings emphasize that saturation status and chain length are important factors to consider when examining the role that LCACoAs play in controlling insulin action in skeletal muscle.

    Previous experiments have studied the effects of weight loss on muscle lipid content. Using quantitative histochemical staining, Goodpaster et al. (28) reported that intramuscular (vastus lateralis) triglyceride concentration decreased with weight loss (∼ 15 kg) in obese subjects with and without diabetes. Using computed tomography to estimate muscle lipid content, this same research group (29) reported a 36% reduction in muscle lipid content in obese individuals after weight loss. These relatively sparse data indicate that muscle triglyceride content is reduced in obese individuals with weight loss. However, although muscle triglyceride content is negatively associated with insulin action (4–6), it is likely that other intramyocellular components of lipid metabolism have a more mechanistic and direct link with the pathophysiology of insulin resistance. Recent evidence indicates that LCACoA esters play a vital role in controlling carbohydrate metabolism and influence insulin action in skeletal muscle (8,11,14,22,24,25). In support of a relationship between LCACoA and insulin action, correlations between insulin action and muscle LCACoA content have been demonstrated in both rodents (30,31) and humans (11). However, the present data are the first, to our knowledge, to demonstrate that LCACoA content is reduced in human skeletal muscle with an intervention that concomitantly enhances insulin action.

    Although cytosolic triglyceride concentration may serve as an useful index of muscle fat content, an accurate determination of intramuscular triglyceride concentration is technically difficult because of possible contamination from adipose tissue interspersed between individual muscle cells (4,11,32). The concentrations of LCACoAs of various chain lengths and saturations are virtually undetectable in adipose tissue; the measurement of LCACoA thus has been proposed as a reliable indicator of intramuscular lipid content (11). In support of LCACoA reflecting muscle lipid content, high-fat feedings increased LCACoA concentration in rodent skeletal muscle (11,33). In addition, tissue-specific overexpression of lipoprotein lipase in liver and muscle promoted increased fatty acyl CoA deposition in these tissues, which was associated with tissue-specific insulin resistance (3). The decrease in LCACoA reported in the current study with weight loss thus also indicates that total intramyocellular lipid content was significantly reduced with this intervention in obese individuals.

    In summary, increases in intramyocellular LCACoAs have been implicated in the pathogenesis of insulin resistance in skeletal muscle. In the present study, muscle palmityl CoA (−35%), stearate CoA (−17%), and linoleate CoA (−30%) decreased significantly with weight loss in obese subjects. Conversely, muscle palmitoleate CoA and oleate CoA were not significantly altered. There was a trend for a larger decrease in palmityl acyl CoA to be associated with enhanced insulin action with weight loss. These findings suggest that a reduction in intramuscular LCACoA content may be responsible, at least in part, for the enhanced insulin action observed with weight loss in obese individuals.

    FIG. 1.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIG. 1.

    Individual and mean body mass (A) and BMI (B) before and after weight (wt.) loss intervention (n = 12; means ± SE). *Significantly different (P < 0.001) from before weight loss.

    FIG. 2.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIG. 2.

    Changes in individual and mean fasting glucose (A), fasting insulin (B), and insulin SI derived from an intravenous glucose tolerance test (C) with weight (wt.) loss. Fasting data are from 12 subjects, and SI data are from 11 subjects (means ± SE). * Significantly different (P < 0.01) from before weight loss.

    FIG. 3.
    • Download figure
    • Open in new tab
    • Download powerpoint
    FIG. 3.

    Changes in individual and mean muscle LCACoA content with weight (wt.) loss. A: Data for 16-chain LCACoAs. B: Data for 18-chain LCACoAs. C: data for total muscle LCACoA content (n = 11; means ± SE). *Significantly different (P < 0.01) from before weight loss for that LCACoA species.

    View this table:
    • View inline
    • View popup
    TABLE 1

    Selected characteristics of the morbidly obese subjects before intervention

    Acknowledgments

    This research was supported by grants from the National Institutes of Health (DK56112 to J.A.H. and DK49230 and DK45735 to G.I.S.).

    Footnotes

    • Address correspondence and reprint requests to Joseph A. Houmard, Human Performance Laboratory, Room 371, Ward Sports Medicine Building, East Carolina University, Greenville, NC 27858. E-mail: houmardj{at}mail.ecu.edu.

      Received for publication 7 February 2002 and accepted in revised form 5 June 2002.

      HOMA, homeostasis model assessment; LCACoA, long-chain fatty acyl-CoA; SI, sensitivity index.

    • DIABETES

    REFERENCES

    1. ↵
      Kraegen EW, Cooney GJ, Ye JM, Thompson AL, Furler SM: The role of lipids in the pathogenesis of muscle insulin resistance and beta cell failure in type II diabetes and obesity. Exp Clin Endocrinol Diabetes109 (Suppl. 2) :S189 –S201,2001
    2. Kim JK, Gavrilova O, Chen Y, Reitman ML, Shulman GI: Mechanism of insulin resistance in A-ZIP/F-1 fatless mice. J Biol Chem275 :8456 –8460,2000
      OpenUrlAbstract/FREE Full Text
    3. ↵
      Kim JK, Fillmore JJ, Chen Y, Yu C, Moore IK, Pypaert M, Lutz EP, Kako Y, Velez-Carrasco W, Goldberg IJ, Breslow JL, Shulman GI: Tissue-specific overexpression of lipoprotein lipase causes tissue-specific insulin resistance. Proc Natl Acad Sci U S A98 :7522 –7527,2001
      OpenUrlAbstract/FREE Full Text
    4. ↵
      Pan DA, Lillioja S, Kriketos AD, Milner MR, Baur LA, Bogardus C, Jenkins AB, Storlien LH: Skeletal muscle triglyceride levels are inversely related to insulin action. Diabetes46 :983 –988,1997
      OpenUrlAbstract/FREE Full Text
    5. ↵
      Krssak M, Falk Peterson K, Dressner A, DiPietro L, Vogel SM, Rothman DL, Shulman GI, Roden M: Intramyocellular lipid concentrations are correlated with insulin sensitivity in humans: a 1H NMR spectroscopy study. Diabetologia42 :113 –116,1999
      OpenUrlCrossRefPubMedWeb of Science
    6. ↵
      Perseghin G, Scifo P, De Cobelli F, Pagliato E, Battezzati A, Arcelloni C, Vanzulli A, Gestolin G, Pozza G, Del Maschio A, Luzi L: Intramyocellular triglyceride content is a determinant of in vivo insulin resistance in humans. Diabetes48 :1600 –1606,1999
      OpenUrlAbstract
    7. ↵
      Jacob S, Machann J, Rett K, Bretchel K, Volk A, Renn W, Maerker E, Matthaei S, Schick F, Claussen CD, Harring HU: Association of increased intramyocellular lipid content with insulin resistance in lean nondiabetic offspring of type 2 diabetic subjects. Diabetes48 :1113 –1119,1999
      OpenUrlAbstract
    8. ↵
      Prentki M, Corkey BE: Are the β-cell signaling molecules malonyl CoA and cytosolic long-chain Acyl-CoA implicated in multiple tissue defects of obesity and NIDDM? Diabetes45 :273 –283,1996
      OpenUrlAbstract/FREE Full Text
    9. ↵
      Corkey BE, Deeney JT, Yaney GC, Tornhelm K, Prentki M: The role of long-chain fatty acyl-CoA esters in β-cell signal transduction. J Nutr130 :299S –304S,2000
    10. ↵
      Corkey BE, Deeney JT: Acyl CoA regulation of metabolism and signal transduction. Prog Clin Biol Res321 :217 –232,1990
      OpenUrlPubMed
    11. ↵
      Ellis BA, Poynten A, Lowy AJ, Furler SM, Chisholm DJ, Kraegen EW, Cooney GJ: Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle. Am J Physiol279 :E554 –E560,2000
      OpenUrlWeb of Science
    12. ↵
      Pories WJ, Swanson MS, MacDonald KG, Long SB, Morris PG, Brown BM, Barakat HA, deRamon RA, Israel RG, Dolezal JM, Dohm GL: Who would have thought it? An operation proves to be the most effective therapy for adult-onset diabetes mellitus. Ann Surg222 :339 –352,1995
      OpenUrlCrossRefPubMedWeb of Science
    13. ↵
      Stein DT, Stevenson BE, Chester MW, Basit M, Daniels MB, Turley SD, McGarry JD: The insulinotropic potency of fatty acids is influenced profoundly by their chain length and degree of saturation. J Clin Invest100 :398 –403,1997
      OpenUrlCrossRefPubMedWeb of Science
    14. ↵
      Yaney GC, Korchak HM, Corkey BE: Long-chain acyl CoA regulation of protein kinase C and fatty acid potentiation of glucose-stimulated insulin secretion in clonal β-cells. Endocrinology141 :1989 –1998,2000
      OpenUrlCrossRefPubMedWeb of Science
    15. ↵
      Bergman RN, Finegood DT, Ader M: Assessment of insulin sensitivity in vivo. Endocr Rev6 :45086 ,1985
      OpenUrl
    16. ↵
      Bonora E, Kiechi S, Willeit J, Oberhollenzer F, Egger G, Targher G, Alberiche M, Bonadonna RC, Muggeo M: Prevalence of insulin resistance in metabolic disorders. Diabetes47 :1643 –1649,1998
      OpenUrlAbstract
    17. ↵
      Bligh EG, Dryer WJ: A rapid method of total lipid extraction and purification. Can J Biochem37 :911 –917,1959
      OpenUrlCrossRefPubMed
    18. ↵
      Neschen S, Moore I, Regittnig W, Yu CL, Wang Y, Pypaert M, Petersen KF, Shulman GI: Contrasting effects of fish oil and safflower oil on hepatic peroxisomal and tissue lipid content. Am J Physiol282 :E395 –E401,2002
      OpenUrlAbstract/FREE Full Text
    19. ↵
      Itani SI, Zhou Q, Pories WJ, MacDonald KG, Dohm GL: Involvement of protein kinase C in human skeletal muscle insulin resistance and obesity. Diabetes49 :1353 –1358,2000
      OpenUrlAbstract
    20. ↵
      Griffin ME, Marcucci MJ, Cline GW, Bell K, Barrucci N, Lee D, Goodyear LJ, Kraegen EW, White MF, Shulman GI: Free fatty acid-induced insulin resistance is associated with activation of protein kinase C θ and alterations in the insulin signaling cascade. Diabetes48 :1270 –1274,1999
      OpenUrlAbstract
    21. ↵
      Dresner A, Laurent D, Marcucci M, Griffin ME, Dufour S, Cline GW, Slezak LA, Andersen DK, Hundal RS, Rothman DL, Petersen KF, Shulman GI: Effects of free fatty acids on glucose transport and IRS-1-associated phosphatidylinositol 3-kinase activity. J Clin Invest103 :252 –259,1999
      OpenUrl
    22. ↵
      Shulman GI: Cellular mechanisms of insulin resistance. J Clin Invest106 :171 –176,2000
      OpenUrlCrossRefPubMedWeb of Science
    23. Aguirre V, Uchida T, Yenush L, Davis R, White M: The c-Jun NH2-terminal kinase promotes insulin resistance during association with insulin receptor substrate-1 and phosphorylation of Ser307. J Biol Chem275 :9047 –9054,2000
      OpenUrlAbstract/FREE Full Text
    24. ↵
      Faergeman NJ, Knudsen J: Role of long-chain fatty acyl-CoA esters in the regulation of metabolism and in cell signaling. Biochem J323 :1 –12,1997
    25. ↵
      Wititsuwannakul D, Kim KH: Mechanism of palmityl coenzyme A inhibition of liver glycogen synthase. J Biol Chem I252 :7812 –7817,1977
      OpenUrlAbstract/FREE Full Text
    26. ↵
      Thompson AL, Cooney GJ: Acyl-CoA inhibition of hexokinase in rat and human skeletal muscle is a potential mechanism of lipid-induced insulin resistance. Diabetes49 :1761 –1765,2000
      OpenUrlAbstract
    27. ↵
      Hannah JS, Howard BV: Dietary fats, insulin resistance, and diabetes. J Cardiovasc Risk1 :31 –37,1994
      OpenUrlPubMed
    28. ↵
      Goodpaster BH, Theriault R, Watkins SC, Kelley DE: Intramuscular lipid content is increased in obesity and decreased by weight loss. Metabolism49 :467 –472,2000
      OpenUrlCrossRefPubMedWeb of Science
    29. ↵
      Goodpaster BH, Thaete FL, Kelley DE: Thigh adipose tissue distribution is associated with insulin resistance in obesity and in type 2 diabetes mellitus. Am J Clin Nutr71 :885 –892,2000
      OpenUrlAbstract/FREE Full Text
    30. ↵
      Oakes ND, Bell KS, Furler SM, Camilleri S, Saha AK, Ruderman NB, Chisholm NJ, Kraegen EW: Diet-induced muscle insulin resistance in rats is ameliorated by acute lipid withdrawal or a single bout of exercise. Diabetes46 :2022 –2028,1997
      OpenUrlAbstract/FREE Full Text
    31. ↵
      Oakes ND, Cooney GJ, Camilleri S, Chisholm DJ, Kraegen EW: Mechanisms of liver and muscle insulin resistance induced by chronic high-fat feeding. Diabetes46 :1768 –1774,1997
      OpenUrlAbstract/FREE Full Text
    32. ↵
      Wendling PS, Peters SJ, Heigenhauser GJ, Spriet LL: Variability of triacylglycerol content in human skeletal muscle biopsy samples. J Appl Physiol81 :1150 –1155,1996
      OpenUrlAbstract/FREE Full Text
    33. ↵
      Chen M-T, Kaufman LN, Spennetta T, Shrago E: Effects of high-fat feeding to rats on the interrelationship of body weight, plasma insulin, and fatty acyl-coenzyme A esters in liver and skeletal muscle. Metabolism41 :564 –569,1992
      OpenUrlCrossRefPubMedWeb of Science
    PreviousNext
    Back to top

    In this Issue

    October 2002, 51(10)
    • Table of Contents
    • Index by Author
    Sign up to receive current issue alerts
    View Selected Citations (0)
    Print
    Download PDF
    Article Alerts
    Sign In to Email Alerts with your Email Address
    Email Article

    Thank you for your interest in spreading the word about Diabetes.

    NOTE: We only request your email address so that the person you are recommending the page to knows that you wanted them to see it, and that it is not junk mail. We do not capture any email address.

    Enter multiple addresses on separate lines or separate them with commas.
    Effect of Weight Loss on Insulin Sensitivity and Intramuscular Long-Chain Fatty Acyl-CoAs in Morbidly Obese Subjects
    (Your Name) has forwarded a page to you from Diabetes
    (Your Name) thought you would like to see this page from the Diabetes web site.
    CAPTCHA
    This question is for testing whether or not you are a human visitor and to prevent automated spam submissions.
    Citation Tools
    Effect of Weight Loss on Insulin Sensitivity and Intramuscular Long-Chain Fatty Acyl-CoAs in Morbidly Obese Subjects
    Joseph A. Houmard, Charles J. Tanner, Chunli Yu, Paul G. Cunningham, Walter J. Pories, Kenneth G. MacDonald, Gerald I. Shulman
    Diabetes Oct 2002, 51 (10) 2959-2963; DOI: 10.2337/diabetes.51.10.2959

    Citation Manager Formats

    • BibTeX
    • Bookends
    • EasyBib
    • EndNote (tagged)
    • EndNote 8 (xml)
    • Medlars
    • Mendeley
    • Papers
    • RefWorks Tagged
    • Ref Manager
    • RIS
    • Zotero
    Add to Selected Citations
    Share

    Effect of Weight Loss on Insulin Sensitivity and Intramuscular Long-Chain Fatty Acyl-CoAs in Morbidly Obese Subjects
    Joseph A. Houmard, Charles J. Tanner, Chunli Yu, Paul G. Cunningham, Walter J. Pories, Kenneth G. MacDonald, Gerald I. Shulman
    Diabetes Oct 2002, 51 (10) 2959-2963; DOI: 10.2337/diabetes.51.10.2959
    del.icio.us logo Digg logo Reddit logo Twitter logo CiteULike logo Facebook logo Google logo Mendeley logo
    • Tweet Widget
    • Facebook Like
    • Google Plus One

    Jump to section

    • Article
      • Abstract
      • RESEARCH DESIGN AND METHODS
      • RESULTS
      • DISCUSSION
      • Acknowledgments
      • Footnotes
      • REFERENCES
    • Figures & Tables
    • Info & Metrics
    • PDF

    Related Articles

    Cited By...

    More in this TOC Section

    • Placental Insulin/IGF-1 Signaling, PGC-1α, and Inflammatory Pathways Are Associated With Metabolic Outcomes at 4–6 Years of Age: The ECHO Healthy Start Cohort
    • Defective FXR-SHP Regulation in Obesity Aberrantly Increases miR-802 Expression, Promoting Insulin Resistance and Fatty Liver
    • Deficiency of Stat1 in CD11c+ Cells Alters Adipose Tissue Inflammation and Improves Metabolic Dysfunctions in Mice Fed a High-Fat Diet
    Show more Obesity Studies

    Similar Articles

    Navigate

    • Current Issue
    • Online Ahead of Print
    • Scientific Sessions Abstracts
    • Collections
    • Archives
    • Submit
    • Subscribe
    • Email Alerts
    • RSS Feeds

    More Information

    • About the Journal
    • Instructions for Authors
    • Journal Policies
    • Reprints and Permissions
    • Advertising
    • Privacy Policy: ADA Journals
    • Copyright Notice/Public Access Policy
    • Contact Us

    Other ADA Resources

    • Diabetes Care
    • Clinical Diabetes
    • Diabetes Spectrum
    • Scientific Sessions Abstracts
    • Standards of Medical Care in Diabetes
    • BMJ Open - Diabetes Research & Care
    • Professional Books
    • Diabetes Forecast

     

    • DiabetesJournals.org
    • Diabetes Core Update
    • ADA's DiabetesPro
    • ADA Member Directory
    • Diabetes.org

    © 2021 by the American Diabetes Association. Diabetes Print ISSN: 0012-1797, Online ISSN: 1939-327X.