Anne-Sophie Morisset

Regional differences in adipose tissue metabolism in women : Minor effect of obesity and body fat distribution

Studies comparing adipose tissue metabolism in central versus peripheral fat depots have generated equivocal data. We examined whether regional differences in abdominal subcutaneous and omental adipose tissue metabolism in women exist and whether they persist across the spectrum of body fatness and abdominal adiposity values. We measured adipocyte size; lipoprotein lipase (LPL) activity; and basal, isoproterenol-, forskolin-, and dibutyryl cAMP–stimulated lipolysis in adipose tissue or mature adipocytes isolated from the omental and subcutaneous fat depots in a sample of 55 healthy women undergoing elective gynecological surgery. Measures of body fat mass and body fat distribution were also obtained by dual-energy X-ray absorptiometry and computed tomography. Subcutaneous adipocytes were significantly larger than omental adipocytes (P < 0.0001). LPL activity expressed as a function of cell number was significantly higher in subcutaneous versus omental adipose tissue (P < 0.0001). Basal, isoproterenol-stimulated, dibutyryl cAMP–stimulated (10−3 mol/l) and forskolin-stimulated (10−5 mol/l) lipolysis (expressed as a function of cell number) were all significantly higher in subcutaneous versus omental adipocytes (P < 0.05 to P < 0.0001). However, the response of omental adipocytes to lipolytic stimuli tested (fold increase over basal level) was significantly greater in magnitude compared with subcutaneous adipocytes (P < 0.01). These differences were relatively constant across total body fat mass and visceral adipose tissue area tertiles. In conclusion, compared with adipocytes from the omental fat compartment, subcutaneous adipocytes are larger, have higher LPL activity, and are more lipolytic on an absolute basis, which may reflect a higher fat storage capacity in this depot in women. In contrast, omental adipocytes display greater relative responsiveness to both adrenergic receptor–and postreceptor-acting agents compared with subcutaneous adipocytes. Overall and visceral obesity have only minor effects on regional differences in adipose tissue metabolism.

Prevention of gestational diabetes mellitus: a review of studies on weight management.

Entering pregnancy with overweight, obesity or gaining excessive gestational weight could increase the risk of gestational diabetes mellitus (GDM), which is associated with negative consequences for both the mother and the offspring. The objective of this article was to review scientific evidence regarding the association between obesity and GDM, and how weight management through nutritional prevention strategies could prove successful in reducing the risk for GDM. Studies published between January 1975 and January 2009 on the relationship between GDM, pre‐pregnancy body mass index (BMI), gestational weight gain and nutritional prevention strategies were included in this review. Results from these reports suggest that maternal obesity assessed by pre‐pregnancy BMI is associated with an increased risk of GDM. They also show an association between gestational weight gain and increased risk for GDM. Higher dietary fat and lower carbohydrate intakes during pregnancy appear to be associated with a higher risk for GDM, independent of pre‐pregnancy BMI. Some studies showed that restricting energy and carbohydrates could minimize gestational weight gain. However, a firm conclusion on the most effective nutritional intervention for the control of gestational weight gain and glycaemic responses could not be reached based on available studies. In light of the studies reviewed, we conclude that weight management through nutritional prevention strategies could be successful in reducing the risk of GDM. Further studies are required to identify the most effective diet composition to prevent GDM and excessive gestational weight gain. Copyright

Elevated Serum 25(OH)D Concentrations, Vitamin D, and Calcium Intakes Are Associated With Reduced Adipocyte Size in Women

Recent studies have suggested a beneficial effect of vitamin D and calcium on adipocyte metabolism and the metabolic profile. Our objective was to examine associations of vitamin D intake, calcium and dairy products as well as serum 25(OH)D concentration with adiposity measures and adipocyte size in women. Omental and subcutaneous adipose tissue samples were obtained from 43 women undergoing gynecological surgeries. Adipocyte size was measured using adipocyte suspensions from collagenase‐digested fat tissues. Total and visceral adiposity were assessed by dual‐energy X‐ray absorptiometry and computed tomography, respectively. Serum 25(OH)D was measured by radioimmmunoassay. Dietary intakes were assessed using a food frequency questionnaire. Women consuming two or more dairy product portions daily had smaller adipocytes in the omental depot compared to women consuming less than two portions daily (79 ± 12 vs. 94 ± 16 µm, P ≤ 0.01). Dietary intakes of calcium (r = −0.55) and vitamin D (r = −0.43) as well as serum 25(OH)D (r = −0.35) were also inversely and significantly associated with omental adipocyte size (P ≤ 0.05 for all). Dietary vitamin D intake was inversely associated with visceral adipose tissue area (r = −0.34, P ≤ 0.05). Serum 25(OH)D was also inversely associated with visceral adipose tissue area (r = −0.32) as well as with total adipose tissue area (r = −0.44), subcutaneous adipose tissue area (r = −0.36), BMI (r =−0.43) and total body fat mass (r = −0.41, P ≤ 0.05 for all). In conclusion, elevated dietary vitamin D intake and serum 25(OH)D values are related to lower visceral adiposity and omental adipocyte size in women.

Weight Gain Measures in Women with Gestational Diabetes Mellitus

BACKGROUND Gestational diabetes mellitus (GDM) and excessive gestational weight gain have significant implications for the health of both mother and child. Our objective was to detail gestational weight gain in women in relationship to GDM. METHODS Data were collected by retrospective reviews of medical records in women who delivered between January and December 2007 at the Laval University Medical Center (Quebec, Canada). The analysis included 294 women (55 GDM and 239 controls) for whom gestational weight gain was calculated by the difference between maternal weight measured at delivery, or at the last prenatal visit (≥37th week), and prepregnancy self-reported weight. Gestational weight gain and rate of weight gain were also calculated for each trimester and until GDM screening. Gestational weight gain was compared to the 2009 recommendations by the Institute of Medicine (IOM). Women with GDM were diagnosed and treated according to the Canadian Diabetes Association guidelines. RESULTS Weight gain in the first trimester was significantly higher in GDM patients compared to controls (3.40 ± 0.42 vs. 1.87 ± 0.16 kg, p ≤ 0.01) and was above IOM recommendations, whereas weight gain in the third trimester was significantly lower in GDM patients compared to controls (4.11 ± 0.36 vs. 6.35 ± 0.18 kg, p ≤ 0.0001). Prepregnancy body mass index (BMI) and first trimester weight gain were both significant and independent predictors of GDM (odds ratio [OR] 1.11, 95% confidence interval [CI] 1.05-1.17, and OR 1.25, 95% CI 1.10-1.42, respectively). CONCLUSIONS First trimester gestational weight gain may need more clinical attention, as it has been identified as an independent and significant risk factor for GDM independent of traditional risk factors, including preconception obesity.

Circulating interleukin-6 concentrations during and after gestational diabetes mellitus.

Objective. Recent studies have shown that high interleukin‐6 (IL‐6) secretion may aggravate insulin resistance in pregnancy and participate in the pathogenesis of gestational diabetes mellitus (GDM). The aim of this study was to determine whether the presence of GDM is associated with elevated IL‐6 concentrations and whether this association remains after delivery, independent of body mass index. Design. Longitudinal study. Setting. Hospital‐based. Sample. Forty‐seven women were screened for GDM with a 75g oral glucose tolerance test at 26.1±3.7 weeks of pregnancy following the Canadian Diabetes Association guidelines (20 GDM, 27 control subjects). Main outcome measures. Interleukin‐6 levels were measured by ELISA at the time of GDM screening and two months post‐partum. Results. Interleukin‐6 concentrations were significantly higher in women with GDM compared with control women at the time of GDM screening (1.47±0.72 vs. 0.90±0.32pg/mL, p≤0.01). Similar results were obtained two months post‐partum, where IL‐6 levels remained significantly higher in women with GDM compared with control women (1.88±0.85 vs. 1.41±0.87pg/mL, p≤0.05). Interleukin‐6 concentrations were significantly correlated with the Matsuda insulin sensitivity index, measured at the two time points (r=–0.60, p≤0.01 and r=–0.34, p≤0.05). The Matsuda insulin sensitivity index was an independent and significant predictor of IL‐6 concentrations at the time of GDM screening, explaining 35.6% of the variance (p≤0.0001) in this variable. IL‐6 concentration measured at GDM screening was identified as an independent and significant predictor of post‐partum IL‐6 concentrations, explaining 28.6% of the variance (p≤0.001). Conclusions. These results show that GDM is associated with elevated IL‐6 levels independent of obesity levels, both during pregnancy and after delivery.

Circulating IL‐6 Concentrations and Abdominal Adipocyte Isoproterenol‐stimulated Lipolysis in Women

Objective: To examine the association of plasma interleukin‐6 (IL‐6) concentrations with adiposity and fat cell metabolism in women.

Impact of diet and adiposity on circulating levels of sex hormone-binding globulin and androgens

This review summarizes studies on the effect of various diets on circulating androgen levels and sex hormone-binding globulin (SHBG). Reduced caloric intake leading to significant weight loss increases SHBG levels regardless of diet composition, particularly in women. Cross-sectional studies show that dietary composition is generally not associated with SHBG levels independent of obesity level. No clear conclusion can be reached regarding the effect of various eating habits or dietary composition on circulating androgens. The evidence indicates that dietary effects on circulating SHBG, and possibly androgens, can be expected if body weight or fatness and/or insulin homeostasis are modulated.

A birth cohort study to investigate the association between prenatal phthalate and bisphenol A exposures and fetal markers of metabolic dysfunction

BackgroundObesity and type-2 diabetes are on the rise and in utero exposure to environmental contaminants is a suspected contributing factor. Our objective was to examine associations between prenatal exposure to potential endocrine disrupting chemicals and markers of fetal metabolic dysfunction.MethodsThe Maternal-Infant Research on Environmental Chemicals Study (MIREC) recruited 2001 women during the first trimester of pregnancy from 10 Canadian sites. First trimester maternal urine was measured for 11 phthalate metabolites and bisphenol A (BPA). Leptin and adioponectin measured in 1,363 available umbilical cord blood samples served as markers of metabolic function. Restricted cubic spline curves were used to assess the relationship between continuous measures of phthalate and BPA levels and cord blood adipokines. Polytomous logistic regression models were used to estimate odds ratios (OR) and 95% confidence intervals (CI) for the association between phthalates and BPA and both high (≥90th percentile) and low (≤10th percentile) fetal adiponectin and leptin, adjusting for confounding factors. Analyses were conducted for all subjects, overall, and separately by fetal sex.ResultsLeptin was significantly higher in female than male infants. We observed an inverse, non-linear relationship between BPA and adiponectin among males in the restricted cubic spline and linear regression analysis. Mono-(3-carboxypropyl) (MCPP) was associated with increased odds of high leptin among males in the polytomous logistic regression models (4th quartile OR = 3.5 95% CI: 1.1-11.6).ConclusionOur findings contribute to the growing body of evidence examining the influence of early life exposure on metabolic regulation and function. Associations between maternal exposure to chemicals and markers of metabolic function appear to be potentially sex specific. However, further investigation is required to determine whether in utero and childhood exposure to BPA and phthalates are associated with metabolic dysfunctions later in life.

Exposure to organophosphorus and organochlorine pesticides, perfluoroalkyl substances, and polychlorinated biphenyls in pregnancy and the association with impaired glucose tolerance and gestational diabetes mellitus: The MIREC Study.

BACKGROUND Studies report increases in rates of gestational diabetes mellitus (GDM) over recent decades. Environmental chemicals may increase the risk of diabetes through impacts on glucose metabolism, mitochondrial dysfunction, and endocrine-disrupting mechanisms including effects on pancreatic β-cell function and adiponectin release. OBJECTIVES To determine the associations between pesticides, perfluoroalkyl substances (PFASs) and polychlorinated biphenyls (PCBs) measured in early pregnancy and impaired glucose tolerance (IGT) and GDM in a Canadian birth cohort. METHODS Women enrolled in the Maternal-Infant Research on Environmental Chemicals (MIREC) Study were included if they had a singleton delivery and did not have pre-existing diabetes. Exposure variables included three organophosphorus (OP) pesticide metabolites detected in first-trimester urine samples, as well as three organochlorine (OC) pesticides, three PFASs, and four PCBs in first-trimester blood samples. Gestational IGT and GDM were assessed by chart review in accordance with published guidelines. Adjusted logistic regression models were used to calculate odds ratios (ORs) and 95% confidence intervals (CI) for the association between quartiles of environmental chemicals and both gestational IGT and GDM. RESULTS Of the 2001 women recruited into the MIREC cohort, 1274 met the inclusion criteria and had outcome and biomonitoring data available. Significantly lower odds of GDM were observed in the third and fourth quartiles of dimethylphosphate (DMP) and in the fourth quartile of dimethylthiophosphate (DMTP) in adjusted analyses (DMP Q3: OR=0.2, 95% CI=0.1-0.7; DMP Q4: OR=0.3, 95% CI=0.1-0.8; DMTP: OR=0.3, 95% CI=0.1-0.9). Significantly elevated odds of gestational IGT was observed in the second quartile of perfluorohexane sulfonate (PFHxS) (OR=3.5, 95% CI=1.4-8.9). No evidence of associations with GDM or IGT during pregnancy was observed for PCBs or OC pesticides. CONCLUSIONS We did not find consistent evidence for any positive associations between the chemicals we examined and GDM or IGT during pregnancy. We observed statistical evidence of inverse relationships between urine concentrations of DMP and DMTP with GDM. We cannot rule out the influence of residual confounding due to unmeasured protective factors, such as nutritional benefits from fruit and vegetable consumption, also associated with pesticide exposure, on the observed inverse associations between maternal OP pesticide metabolites and GDM. These findings require further investigation.

Impact of a lignan-rich diet on adiposity and insulin sensitivity in post-menopausal women

There has been a growing interest in lignans, a class of phyto-oestrogens, because of their potentially favourable effects on human health. The aim of the present study was to compare the metabolic profile of post-menopausal women consuming various amounts of dietary lignans. Phyto-oestrogen intake was assessed using a 3-d dietary record analysed with a Canadian food phyto-oestrogen content data table in 115 post-menopausal women (age 56.8 (SD 4.4) years and BMI 28.5 (SD 5.9) kg/m(2)). Plasma enterolactone (ENL), the major biologically active metabolite of dietary lignans, was determined by time-resolved fluoroimmunoassay. Anthropometrics, abdominal adipose tissue areas (computed tomography), body composition (hydrostatic weighing) and insulin sensitivity (hyperinsulinaemic-euglycaemic clamp) were measured in all women. Women in the high dietary lignan intake subgroup (n 29) had a significantly lower BMI and total body fat mass, as well as a better glucose disposal rate (GDR; P < 0.05), compared with women in the low lignan intake subgroup (n 28). The majority of women with the highest dietary lignan intake were also in the highest quartile of plasma ENL (59 %). Women in the highest ENL quartile had a significantly lower BMI (26.1 (SD 4.4) v. 30.4 (SD 6.9) kg/m(2), P < 0.05), total body fat mass (24.8 (SD 9.8) v. 33.3 (SD 13.3) kg, P < 0.05), 2 h postload glycaemia (5.5 (SD 0.9) v. 5.7 (sd 0.8) nmol/l, P < 0.05) and a higher GDR (8.3 (SD 2.7) v. 5.5 (SD 2.8), P < 0.01) compared with women in the lowest ENL quartile. In conclusion, women with the highest ENL concentrations had a better metabolic profile including higher insulin sensitivity and lower adiposity measures.