Post-heparin lipolytic enzyme activities, sex hormones and sex hormone-binding globulin (SHBG) in men and women: The HERITAGE Family Study

Desmeules, Annie; Couillard, Charles; Tchernof, André; Bergeron, Jean; Rankinen, Tuomo; Leon, Arthur S.; Rao, D. C.; Skinner, James S.; Wilmore, Jack H.; Després, Jean‐Pierre; Bouchard, Claude

doi:10.1016/j.atherosclerosis.2003.08.018

Cited by 44 publications

(40 citation statements)

References 40 publications

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“…Liver uptake of DFA occurs via direct uptake of chylomicron-remnant particles, hepatic lipasemediated hydrolysis of chylomicron-remnant TG, and recirculation into plasma NEFA after adipose tissue lipolysis. The absence of sex effect on liver DFA partitioning in the current study was observed despite the known increase in hepatic lipase activity in men versus women (25). The lack of IGT, sex, or sex-IGT interaction effect on liver DFA partitioning also occurred despite a significant increase in liver steatosis in IGT + attributable mostly to women (i.e., significant sex-IGT interaction).…”

Section: Discussionmentioning

confidence: 54%

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

et al. 2014

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Oral 14(R,S)-[18 F]-fluoro-6-thia-heptadecanoic acid was used to determine whether an increase in cardiac dietary fatty acid (DFA) metabolism in impaired glucose tolerance (IGT) is different in men and women. Myocardial DFA partitioning after 6 h was higher in IGT versus control subjects (P = 0.006) in both men (2.14 [95% CI sex difference. Men had higher net myocardial DFA uptake between time 90 and 120 min driven by higher chylomicrontriglyceride (TG) levels. IGT-associated increased cardiac DFA partitioning was directly related to obesity in women, whereas it was associated with IGT per se in men. We conclude that early cardiac DFA uptake is higher in men driven by change in postprandial chylomicron-TG level but that increase in 6-h postprandial cardiac DFA partitioning nevertheless occurs with IGT both in men and women.Sex, obesity, and insulin resistance appear to act independently but also in concert on myocardial metabolism, structure, and function. Studies conducted in the fasting state show that women have greater myocardial oxygen consumption (1), which increases with obesity (2). In addition, female sex appears to be an important predictor of higher diabetes-associated cardiac plasma nonesterified fatty acid (NEFA) utilization (3). Excess exposure of lean tissues to fatty acids may stem from a disordered storage of dietary fatty acids (DFAs) in adipocytes (4-7). We recently developed a novel method for noninvasive measurement of organ-specific DFA uptake and partitioning using 14(R,S)-[ 8). Using this method, we found that subjects with impaired glucose tolerance (IGT) displayed increased myocardial DFA partitioning and fractional uptake that correlated negatively with left ventricular ejection fraction (9). Subjects with IGT also displayed reduced DFA partitioning in abdominal adipose tissues (9), in accordance with findings using conventional tracer methods (10-12).Due to the small sample size at the time of our previous report, it was not possible to assess whether any sexrelated differences in organ-specific DFA metabolism were present and could modulate the effect of IGT on cardiac metabolism. Based on previous reports on cardiac NEFA metabolism (3), the hypothesis of the current study was that elevated DFA uptake and partitioning observed with IGT would be worsened in women versus men. A secondary exploratory objective of our study was to determine sexrelated differences in liver, skeletal muscle, and adipose tissue DFA partitioning according to IGT status. RESEARCH DESIGN AND METHODS Study ParticipantsForty-one Caucasian individuals (see Table 1) with normal (IGT 2 ) and IGT (IGT + ), defined as having a 2-h post 75-g

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Section: Discussionmentioning

confidence: 54%

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

et al. 2014

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“…Therefore, it is likely that a high level of SHBG would temper the unfavourable effects of free androgens on the lipoprotein profile. Moreover, activity and expression of hepatic lipase, which is involved in HDL-C catabolism [17], is known to be depressed by estradiol but stimulated by androgens [18,19], independently of insulin and abdominal adiposity [19]. Therefore, a high SHBG would result in a decreased free active testosterone, thus maintaining a low hepatic lipase activity and a high level of HDL-C.…”

Section: Discussionmentioning

confidence: 99%

Sex hormone-binding globulin is a major determinant of the lipid profile: the PRIME study

et al. 2005

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The prevalence of coronary heart disease is much higher in men than in women and sex hormones might play a role in these differences through their influence on the lipid profile. The aim of this cross-sectional study was to study the relationship between hormonal markers (total testosterone (TT), estradiol (E2), sex-hormone-binding globulin (SHBG)) and plasma lipids in a population-based sample. Subjects were 352 men, 50-59 years old, selected in France (Lille, Strasbourg and Toulouse) and Northern-Ireland (Belfast) who had questionnaires and a medical examination at baseline of the PRIME prospective study (1991)(1992)(1993). Pearson correlation coefficients and Student's t tests were used to identify factors associated with plasma lipids. Multiple linear regression models were used for multivariate analyses, using triglycerides (TG) (log-transformed) and high density-lipoprotein cholesterol (HDL-C) as dependent variables. SHBG and TT were negatively correlated with TG (p < 0.0001 and p < 0.05, respectively) and positively correlated with HDL-C (p < 0.0001 and p < 0.01). E2 was positively correlated with TG (p < 0.05). No significant association was found between sex-hormones and LDL-C. In multiple linear regression analyses, SHBG remained independently associated negatively with TG (p < 0.01) and positively with HDL-C (p < 0.0001) after adjustment for centre of recruitment, age, body mass index, systolic blood pressure, smoking, alcohol intake and physical activity. After further adjustment for insulin, the association between SHBG and HDL-C remained highly significant (p < 0.0001). The association between SHBG and TG was weakened but remained also significant. Our results suggest that SHBG might to be a central protein in the hormonal regulation of the lipid profile.

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“…83 The sensitivity of lipolytic enzymes for androgens is further supported by findings from the HERITAGE study showing a strong inverse association between SHBG and HL activity and a positive association between SHBG and LPL activity. 106 Apart from direct regulatory effects, testosterone and SHBG may also influence lipid metabolism indirectly through their associations with obesity. Yasui et al 60 found that associations of SHBG with HDL-C and triglycerides were no longer significant after controlling for BMI.…”

Section: Lipid Profilementioning

confidence: 99%

Testosterone, SHBG and cardiovascular health in postmenopausal women

Brand

Schouw

2010

Int J Impot Res

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Cardiovascular disease (CVD) affects men and women differently with women having a lower incidence and later onset of disease. Research has recently refocused interest on the cardiovascular role of androgens. The purpose of this review is to summarize the evidence available on the association between testosterone and cardiovascular health in postmenopausal women. Published studies relating testosterone and sex hormone-binding globulin (SHBG) to CVD and its risk factors were reviewed. Studies included in this review suggest that increased androgenicity, characterized by high testosterone and low SHBG levels, is associated with an adverse CVD risk factor profile in postmenopausal women. However, evidence for an association with cardiovascular events is lacking and it is uncertain whether the observed associations with endogenous testosterone have clinical implications regarding the use of postmenopausal testosterone therapy. Large-scale, longitudinal studies relating testosterone and SHBG levels to cardiovascular risk factors and endpoints are needed to determine the temporal relationship between androgenicity and cardiovascular risk and to ascertain the long-term efficacy and safety of testosterone therapy in postmenopausal women.

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Post-heparin lipolytic enzyme activities, sex hormones and sex hormone-binding globulin (SHBG) in men and women: The HERITAGE Family Study

Cited by 44 publications

References 40 publications

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

Effect of Sex and Impaired Glucose Tolerance on Organ-Specific Dietary Fatty Acid Metabolism in Humans

Sex hormone-binding globulin is a major determinant of the lipid profile: the PRIME study

Testosterone, SHBG and cardiovascular health in postmenopausal women

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