Intravenous Lipid and Heparin Infusion-Induced Elevation in Free Fatty Acids and Triglycerides Modifies Circulating Androgen Levels in Women: A Randomized, Controlled Trial

Mai, Knut; Bobbert, Thomas; Reinecke, Franziska; Andres, Janin; Maser-Gluth, Christiane; Wudy, Stefan A.; Möhlig, Matthias; Weickert, Martin O.; Hartmann, Michaela F.; Schulte, Heinrich M.; Diederich, S.; Pfeiffer, Andreas F. H.; Spranger, Joachim

doi:10.1210/jc.2008-0714

Cited by 49 publications

(35 citation statements)

References 34 publications

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“…Accumulation of plasma fatty acids in muscle and liver tissues induce mitochondrial dysfunction, oxidative stress, inflammation and immune disorders [84]. On the other hand, high circulating FFA levels have been shown in vivo to increase the production of all androgens in normal women [85]. Another study found that male rats fed on a high monounsaturated fatty acid (MUFA) diet for 6 weeks display increased testosterone levels (vs. low MUFA diet), and that free fatty acid with different degree of saturation increased testosterone levels to significantly different extent [86].…”

Section: Cellular Mechanisms Of Metabolic Insulin Resistance-mostmentioning

confidence: 99%

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Baptiste

Battista

Trottier

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

266

199

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Polycystic ovary syndrome (PCOS) is a very common endocrine disorder characterized by chronic anovulation, clinical and/or biochemical hyperandrogenism, and/or polycystic ovaries. But most experts consider that hyperandrogenism is the main characteristic of PCOS. Several theories propose different mechanisms to explain PCOS manifestations: (1) a primary enzymatic default in the ovarian and/or adrenal steroidogenesis; (2) an impairment in gonadotropin releasing hormone (GnRH) secretion that promotes luteal hormone (LH) secretion; or (3) alterations in insulin actions that lead to insulin resistance with compensatory hyperinsulinemia. However, in the past 20 years there has been growing evidence supporting that defects in insulin actions or in the insulin signalling pathways are central in the pathogenesis of the syndrome. Indeed, most women with PCOS are metabolically insulin resistant, in part due to genetic predisposition and in part secondary to obesity. But some women with typical PCOS do not display insulin resistance, which supports the hypothesis of a genetic predisposition specific to PCOS that would be revealed by the development of insulin resistance and compensatory hyperinsulinemia in most, but not all, women with PCOS. However, these hypotheses are not yet appropriately confirmed, and more research is still needed to unravel the true pathogenesis underlying this syndrome. The present review thus aims at discussing new concepts and findings regarding insulin actions in PCOS women and how it is related to hyperandrogenemia.

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Section: Cellular Mechanisms Of Metabolic Insulin Resistance-mostmentioning

confidence: 99%

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Baptiste

Battista

Trottier

et al. 2010

The Journal of Steroid Biochemistry and Molecular Biology

266

199

View full text Add to dashboard Cite

show abstract

“…A controlled, randomized, crossover trial has shown an increase in adrenal androgen precursors DHEA, DHEAS, androstenedione, and in androgens testosterone and 5α-dihydrotestosterone during lipid infusion in healthy young women [37]; this effect appears to be independent of subsequent changes in insulin sensitivity.…”

Section: Discussionmentioning

confidence: 99%

Saturated Fat Intake Is Related to Heart Rate Variability in Women with Polycystic Ovary Syndrome

Graff¹,

Mario²,

Magalhães³

et al. 2017

Ann Nutr Metab

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Background/Aims: There is a heightened risk for cardiovascular diseases in women with polycystic ovary syndrome (PCOS). Alterations in heart rate variability (HRV) may reflect subclinical cardiovascular disease, with a putative association between HRV and dietary fat. This study evaluated HRV in PCOS and control women based on the dietary intake of saturated fatty acid (SFA). Methods: Biochemical/hormonal profile, resting metabolic rate, physical activity, HRV in response to the Stroop test, and dietary intake were assessed in 84 PCOS and 54 control women stratified by median SFA intake in the PCOS group (8.5% of daily energy intake). Results: Body mass index (p = 0.041), blood pressure (p < 0.01), and HOMA-IR (p = 0.003) were higher in PCOS vs. controls. PCOS women had higher testosterone (p = 0.001), dehydroepiandrosterone sulfate (p = 0.012), and free androgen index (p = 0.001), and lower sex hormone-binding globulin levels than controls (p = 0.001). In both groups, the clinical profile and calorie intake were similar between SFA categories. In PCOS, testosterone was lower when SFA intake <8.5%. PCOS women with SFA <8.5% consumed more beans, fruits, and vegetables and had better frequency and time domain HRV indices. No differences in HRV were detected between SFA categories in controls. In PCOS, age and SFA intake were independent predictors of HRV. Conclusions: Lower SFA intake is related to improved cardiovascular autonomic function in PCOS.

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“…However, the impact of NEFA overexposure on androgen production has been investigated in vivo and in vitro (8 -10). Indeed, it has been shown that increasing NEFA levels experimentally in normal young men and women, using an Lipovenös/heparin infusion, significantly increased androgen levels (8,9), well before any apparent increase in circulating insulin levels. Using bovine adrenal androgen-secreting cells, we recently published that addition of palmitate, a saturated fatty acid, to the cell culture medium significantly increased ACTH-or forskolin-stimulated androgen production (10).…”

Section: Discussionmentioning

confidence: 99%

“…This suggests that metabolic factors contribute more to PCOS hyperandrogenemia than ACTH or LH. Interestingly, lipotoxicity, referring to the cellular adverse consequences of nonesterified fatty acids (NEFA) (6), has been implicated in the development of IR (7), and recent studies have found that increasing circulating NEFA levels also stimulates androgen production in healthy men (8) and women (9). This suggests that systemic NEFA overflow can also trigger androgen production in vivo.…”

mentioning

confidence: 99%

Angiotensin II Type 2 Receptor Stimulation Improves Fatty Acid Ovarian Uptake and Hyperandrogenemia in an Obese Rat Model of Polycystic Ovary Syndrome

et al. 2014

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Polycystic ovary syndrome (PCOS) is mainly defined by hyperandrogenism but is also characterized by insulin resistance (IR). Studies showed that overexposure of nonadipose tissues to nonesterified fatty acids (NEFA) may explain both IR and hyperandrogenism. Recent studies indicate that treatment with an angiotensin II type 2 receptor (AT2R)-selective agonist improves diet-induced IR. We thus hypothesized that PCOS hyperandrogenism is triggered by ovarian NEFA overexposure and is improved after treatment with an AT2R agonist. Experiments were conducted in 12-week-old female JCR:LA-cp/cp rats, which are characterized by visceral obesity, IR, hyperandrogenism, and polycystic ovaries. Control JCR:LA +/? rats have a normal phenotype. Rats were treated for 8 days with saline or the selective AT2R agonist C21/M24 and then assessed for: 1) fasting testosterone, NEFA, and insulin levels; and 2) an iv 14(R,S)-[(18)F]fluoro-6-thia-heptadecanoic acid test to determine NEFA ovarian tissue uptake (Km). Compared with controls, saline-treated PCOS/cp rats displayed higher insulin (100 vs 5.6 μU/mL), testosterone (0.12 vs 0.04 nmol/L), NEFA (0.98 vs 0.48 mmol/L), and Km (20.7 vs 12.9 nmol/g·min) (all P < .0001). In PCOS/cp rats, C21/M24 did not significantly improve insulin or NEFA but normalized testosterone (P = .004) and Km (P = .009), which were strongly correlated together in all PCOS/cp rats (ρ = 0.74, P = .009). In conclusion, in an obese PCOS rat model, ovarian NEFA uptake and testosterone levels are strongly associated and are both significantly reduced after short-term C21/M24 therapy. These findings provide new information on the role of NEFA in PCOS hyperandrogenemia and suggest a potential role for AT2R agonists in the treatment of PCOS.

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Intravenous Lipid and Heparin Infusion-Induced Elevation in Free Fatty Acids and Triglycerides Modifies Circulating Androgen Levels in Women: A Randomized, Controlled Trial

Cited by 49 publications

References 34 publications

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Insulin and hyperandrogenism in women with polycystic ovary syndrome

Saturated Fat Intake Is Related to Heart Rate Variability in Women with Polycystic Ovary Syndrome

Angiotensin II Type 2 Receptor Stimulation Improves Fatty Acid Ovarian Uptake and Hyperandrogenemia in an Obese Rat Model of Polycystic Ovary Syndrome

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