Perilipin polymorphism interacts with saturated fat and carbohydrates to modulate insulin resistance

C. E. Smith, D. K. Arnett, D. Corella, M. Y. Tsai, C. Q. Lai, L. D. Parnell, Y. C. Lee, J. M. Ordovás

Research output: Contribution to journalArticlepeer-review

34 Scopus citations


Background and aims: Macronutrient intakes and genetic variants have been shown to interact to alter insulin resistance, but replications of gene-nutrient interactions across independent populations are rare, despite their critical importance in establishing credibility. We aimed to investigate a previously demonstrated saturated fat and carbohydrate interaction for insulin resistance for perilipin (PLIN1), a regulator of adipocyte metabolism. Methods and results: We investigated the previously shown interaction for PLIN1 11482G > A (rs894160) on insulin resistance in US men (n = 462) and women (n = 508) (mean ± SD, 49 ± 16 years). In multivariable linear regression models, we found an interaction (P < 0.05) between the ratio of saturated fat to carbohydrate intake as a continuous variable and PLIN1 11482G > A for HOMA-IR (homeostasis model assessment of insulin resistance) in women. For carriers of the minor allele but not for non-carriers, as the ratio of saturated fat to carbohydrate intake increased, predicted HOMA-IR increased (P = 0.002). By dichotomizing the ratio of saturated fat to carbohydrate intake into high and low, we found significant interaction terms for insulin and HOMA-IR (P < 0.05). When the ratio of saturated fat to carbohydrate was high, insulin and HOMA-IR were higher in minor allele carriers (P = 0.004 and P = 0.003, respectively), but did not differ when the ratio was low. Similar patterns or trends were observed when saturated fat and carbohydrate were dichotomized into high and low as individual macronutrients. Conclusions: Replication of the previously reported interaction between macronutrient intakes and PLIN1 genotype for insulin resistance reinforces the potential usefulness of applying genotype information in the dietary management of insulin resistance.

Original languageEnglish
Pages (from-to)449-455
Number of pages7
JournalNutrition, Metabolism and Cardiovascular Diseases
Issue number5
StatePublished - May 2012

Bibliographical note

Funding Information:
This work was supported by the National Institutes of Health, National Institute on Aging , Grant Number 5P01AG023394-02 and NIH/NHLBI grant number HL54776 and NIH/NIDDK DK075030 and contracts 53-K06-5–10 and 58–1950-9–001 from the U.S. Department of Agriculture Research Service. C.E. Smith is supported by T32 DK007651-19.


  • Gene-nutrient interaction
  • Insulin resistance
  • Perilipin
  • Replication

ASJC Scopus subject areas

  • Medicine (miscellaneous)
  • Endocrinology, Diabetes and Metabolism
  • Nutrition and Dietetics
  • Cardiology and Cardiovascular Medicine


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