Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome

Frank González, Robert Considine, Ola A. Abdelhadi, Anthony J. Acton

Research output: Contribution to journalArticle

Abstract

Context: Inflammation and insulin resistance (IR) are often present in polycystic ovary syndrome (PCOS). Objective: We determined the effect of saturated fat ingestion on circulating lipopolysaccharide (LPS) and mononuclear cell (MNC) toll-like receptor-4 (TLR-4) and suppressor of cytokine signaling-3 (SOCS-3) in women with PCOS. Design: Cross-sectional study. Setting: Academic medical center. Patients: Nineteen reproductive-age women with PCOS (10 lean, 9 obese) and 19 ovulatory control subjects (10 lean, 9 obese). Main Outcome Measures: LPS and TNFα levels were measured in plasma. TLR-4 and SOCS-3 mRNA and protein content were quantified in MNC from blood collected after fasting and 2, 3, and 5 hours after saturated fat ingestion. Insulin sensitivity was derived from an oral glucose tolerance test (ISOGTT). Androgen secretion was assessed from blood collected after fasting and 24, 48, and 72 hours after human chorionic gonadotropin (HCG) administration. Results: Regardless of PCOS status, subjects who were obese had lipid-induced increases in circulating LPS and TLR-4 protein content compared with subjects who were lean. Lean and obese women with PCOS had lipid-induced increases in plasma TNFα and SOCS-3 mRNA and protein content compared with lean control subjects. Both PCOS groups had lower ISOGTT and greater HCG-stimulated androgen secretion compared with control subjects. The LPS and SOCS-3 responses were negatively correlated with ISOGTT and positively correlated with HCG-stimulated androgen secretion. Conclusion: In PCOS, lipid-induced LPS-mediated inflammation through TLR-4 is associated with obesity and worsened by PCOS, whereas lipid-induced increases in SOCS-3 may represent an obesity-independent, TNFα-mediated mechanism of IR.

Original languageEnglish (US)
Pages (from-to)934-946
Number of pages13
JournalThe Journal of clinical endocrinology and metabolism
Volume104
Issue number3
DOIs
StatePublished - Mar 1 2019

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Polycystic Ovary Syndrome
Toll-Like Receptor 4
Lipopolysaccharides
Insulin Resistance
Eating
Fats
Insulin
Cytokines
Inflammation
Chorionic Gonadotropin
Androgens
Lipids
Blood
Plasmas
Messenger RNA
Proteins
Fasting
Obesity
Glucose Tolerance Test
Glucose

ASJC Scopus subject areas

  • Endocrinology, Diabetes and Metabolism
  • Biochemistry
  • Endocrinology
  • Clinical Biochemistry
  • Biochemistry, medical

Cite this

Saturated Fat Ingestion Promotes Lipopolysaccharide-Mediated Inflammation and Insulin Resistance in Polycystic Ovary Syndrome. / González, Frank; Considine, Robert; Abdelhadi, Ola A.; Acton, Anthony J.

In: The Journal of clinical endocrinology and metabolism, Vol. 104, No. 3, 01.03.2019, p. 934-946.

Research output: Contribution to journalArticle

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