This Article Full Text Full Text (PDF) Submit a related Letter to the Editor Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Copyright Permission Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perseghin, G. Articles by Luzi, L. Search for Related Content PubMed PubMed Citation Articles by Perseghin, G. Articles by Luzi, L.

Gender Factors Affect Fatty Acids-Induced Insulin Resistance in Nonobese Humans: Effects of Oral Steroidal Contraception¹

Divisions of Internal Medicine I (G.P., A.B., S.B., L.L.), Nuclear Medicine (P.S.), Diagnostic Radiology (P.S., A.D.M.), and Laboratory Medicine-Centro San Luigi (L. S.), Unit of Clinical Spectroscopy (G.P., P.S., A.D.M., L.L.), Università Vita e Salute San Raffaele, Istituto Scientifico H San Raffaele, 20132 Milan; and International Center for the Assessment of Nutritional Status, Università degli Studi di Milano (E.P., G.T., L.L.), 20100 Milan, Italy

Address all correspondence and requests for reprints to: Gianluca Perseghin, M.D., Division of Internal Medicine I, Laboratory of Amino Acids and Stable Isotopes/Unit of Clinical Spectroscopy, Via Olgettina 60, 20132 Milan, Italy. E-mail: perseghin.gianluca{at}hsr.it

Abstract

Plasma free fatty acids and intramyocellular triglycerides (IMCL) content modulate whole body insulin sensitivity in humans. To test whether the interactions between fatty acid metabolism and insulin action in nonobese humans are related to gender factors, we studied 15 young, normal weight, healthy men and 15 women matched for life habits and whole body insulin sensitivity, determined with the euglycemic-hyperinsulinemic clamp, by means of indirect calorimetry to assess substrate oxidation, localized ¹H nuclear magnetic resonance spectroscopy of calf muscles to assess IMCL content, and dual energy x-ray absorption to assess body composition. In addition, to test whether perturbation of the feminine hormonal milieu modifies these interactions, we studied 15 matched females using oral steroidal contraception (OSC). Insulin sensitivity in women, notwithstanding increased body fatness, plasma free fatty acids, IMCL content, and circulating ß-hydroxybutyrate levels and reduced lipid oxidation, was similar to that in men. Women using OSC showed a 40% reduction of insulin sensitivity associated with increased plasma free fatty acids, ß-hydroxybutyrate, cholesterol, and triglycerides levels and a slight increment in IMCL content compared with women with intact hormonal cycles. In all groups the IMCL content was inversely related to insulin sensitivity. In conclusion, nonobese, healthy, young women are as insulin sensitive as men, notwithstanding the higher levels of postabsorptive circulating and tissue-stored fatty acids; OSC-induced insulin resistance is associated with abnormal fatty acid metabolism and loss of this gender-related feature.

This article has been cited by other articles:

				G. Perseghin, G. Lattuada, F. De Cobelli, A. Esposito, E. Belloni, T. Canu, F. Ragogna, P. Scifo, A. Del Maschio, and L. Luzi Serum Retinol-Binding Protein-4, Leptin, and Adiponectin Concentrations Are Related to Ectopic Fat Accumulation J. Clin. Endocrinol. Metab., December 1, 2007; 92(12): 4883 - 4888. [Abstract] [Full Text] [PDF]

				M. R. Soeters, H. P. Sauerwein, J. E. Groener, J. M. Aerts, M. T. Ackermans, J. F. C. Glatz, E. Fliers, and M. J. Serlie Gender-Related Differences in the Metabolic Response to Fasting J. Clin. Endocrinol. Metab., September 1, 2007; 92(9): 3646 - 3652. [Abstract] [Full Text] [PDF]

				S. Nader and E. Diamanti-Kandarakis Polycystic ovary syndrome, oral contraceptives and metabolic issues: new perspectives and a unifying hypothesis Hum. Reprod., February 1, 2007; 22(2): 317 - 322. [Abstract] [Full Text] [PDF]

				J. Vrbikova and D. Cibula Combined oral contraceptives in the treatment of polycystic ovary syndrome Hum. Reprod. Update, May 1, 2005; 11(3): 277 - 291. [Abstract] [Full Text] [PDF]

				K.-C. Leung, G. Johannsson, G. M. Leong, and K. K. Y. Ho Estrogen Regulation of Growth Hormone Action Endocr. Rev., October 1, 2004; 25(5): 693 - 721. [Abstract] [Full Text] [PDF]

				X. Ma, S. Bacci, W. Mlynarski, L. Gottardo, T. Soccio, C. Menzaghi, E. Iori, R. A. Lager, A. R. Shroff, E. V. Gervino, et al. A common haplotype at the CD36 locus is associated with high free fatty acid levels and increased cardiovascular risk in Caucasians Hum. Mol. Genet., October 1, 2004; 13(19): 2197 - 2205. [Abstract] [Full Text] [PDF]

				G. Perseghin, G. Lattuada, M. Danna, L. P. Sereni, P. Maffi, F. De Cobelli, A. Battezzati, A. Secchi, A. Del Maschio, and L. Luzi Insulin resistance, intramyocellular lipid content, and plasma adiponectin in patients with type 1 diabetes Am J Physiol Endocrinol Metab, December 1, 2003; 285(6): E1174 - E1181. [Abstract] [Full Text] [PDF]

				L. Piemonti, G. Calori, A. Mercalli, G. Lattuada, P. Monti, M. P. Garancini, F. Costantino, G. Ruotolo, L. Luzi, and G. Perseghin Fasting Plasma Leptin, Tumor Necrosis Factor-{alpha} Receptor 2, and Monocyte Chemoattracting Protein 1 Concentration in a Population of Glucose-Tolerant and Glucose-Intolerant Women: Impact on cardiovascular mortality Diabetes Care, October 1, 2003; 26(10): 2883 - 2889. [Abstract] [Full Text] [PDF]

				L. Luzi, G. Perseghin, G. Tambussi, E. Meneghini, P. Scifo, E. Pagliato, A. Del Maschio, G. Testolin, and A. Lazzarin Intramyocellular lipid accumulation and reduced whole body lipid oxidation in HIV lipodystrophy Am J Physiol Endocrinol Metab, February 1, 2003; 284(2): E274 - E280. [Abstract] [Full Text] [PDF]

				P. Shah, A. Vella, A. Basu, R. Basu, A. Adkins, W. F. Schwenk, C. M. Johnson, K. S. Nair, M. D. Jensen, and R. A. Rizza Elevated Free Fatty Acids Impair Glucose Metabolism in Women: Decreased Stimulation of Muscle Glucose Uptake and Suppression of Splanchnic Glucose Production During Combined Hyperinsulinemia and Hyperglycemia Diabetes, January 1, 2003; 52(1): 38 - 42. [Abstract] [Full Text] [PDF]

				G. Perseghin, P. Scifo, M. Danna, A. Battezzati, S. Benedini, E. Meneghini, A. Del Maschio, and L. Luzi Normal insulin sensitivity and IMCL content in overweight humans are associated with higher fasting lipid oxidation Am J Physiol Endocrinol Metab, September 1, 2002; 283(3): E556 - E564. [Abstract] [Full Text] [PDF]

				B. D. Hegarty, G. J. Cooney, E. W. Kraegen, and S. M. Furler Increased Efficiency of Fatty Acid Uptake Contributes to Lipid Accumulation in Skeletal Muscle of High Fat-Fed Insulin-Resistant Rats Diabetes, May 1, 2002; 51(5): 1477 - 1484. [Abstract] [Full Text] [PDF]

				M. Krebs, M. Krssak, E. Bernroider, C. Anderwald, A. Brehm, M. Meyerspeer, P. Nowotny, E. Roth, W. Waldhausl, and M. Roden Mechanism of Amino Acid-Induced Skeletal Muscle Insulin Resistance in Humans Diabetes, March 1, 2002; 51(3): 599 - 605. [Abstract] [Full Text] [PDF]