Sexual Dimorphism in Body Fat Distribution and Risk for Cardiovascular Diseases

The prevalence of obesity has dramatically increased over the past decade along with the cardiovascular and other health risks it encompasses. Adipose tissue, which is distributed in the abdominal viscera, carries a greater risk for cardiovascular disorders than adipose tissue subcutaneously. There is a sex difference in the regional fat distribution. Women have more subcutaneous fat, whereas men have more visceral fat. Therefore, obesity-related metabolic disorders are much lower in premenopausal women than men. Peripheral metabolic signals like leptin and insulin are involved in the food intake, body weight, body fat distribution, and cardiovascular disease. Key areas in the brain, including the hypothalamus, integrates these peripheral adiposity signals to maintain overall adiposity levels, and these brain regions are directly influenced by sex hormones. Therefore, differences in cardiovascular disease may be under the influence of sex hormones either directly in the brain or through their influence of body fat distribution. The role of estrogen in mediating body fat distribution and cardiovascular disease is the focus of this review.     

Gonadal effects on food intake and adiposity: a metabolic hypothesis.

Ovarian and testicular steroids have important effects on body weight and composition in rats. Estradiol and testosterone decrease adiposity, while progesterone increases carcass fat content. These hormone-induced changes in body weight and composition are accompanied by changes in food intake and voluntary exercise, suggesting that the hormones induce behavioral changes which alter body weight and adiposity. However, several lines of evidence indicate that these behavioral changes are neither necessary nor sufficient to produce the hormone-induced body weight shifts. Rather, peripheral metabolic effects of gonadal steroids may be of primary importance in the control of fat disposition. Steroid effects on triglyceride clearance from circulation, along with changes in hepatic synthesis, may in turn alter the availability of triglycerides as an oxidizable fuel, contributing to the changes in food intake. From this perspective, estradiol- and progesterone-induced changes in food intake are viewed as consequences, rather than causes, of changes in fat metabolism. It is suggested that during naturally-occurring reproductive states gonadal steroids interact with other hormones, such as prolactin, to partition available triglycerides among tissues which oxidize, excrete or store long-chain fatty acids (e.g., striated muscle, mammary gland, or adipose tissue, respectively).     

Leptin does not reduce body fat content but augments cold defense abilities in thermoneutrally reared rat pups

 A previous study showed that recombinant leptin markedly affects the body fat content and thermoregulatory energy expenditure of lean (+/+ and +/fa) suckling-age rats, and we wanted to find out whether leptin in doses that halved body fat of cold-reared lean pups had any effect in thermoneutrally reared lean pups. When +/+ pups were artificially reared from 4 to 16 days of age at thermoneutrality and treated as before with leptin from day 7, their total metabolic rate throughout the treatment period was only 4% higher than that of the control littermates and their final body fat content only 4% lower (both P>0.05). We conclude from comparisons of the results in +/+ pups at cold and thermoneutral conditions that leptin does not stimulate, but rather disinhibits, sympathetically mediated thermoregulatory thermogenesis. Received: 26 February 1997 / Received after revision: 14 July 1997 / Accepted: 17 July 1997     

Transgenerational effects of prenatal exposure to the Dutch famine on neonatal adiposity and health in later life

Objective  Maternal undernutrition during gestation is associated with increased metabolic and cardiovascular disease in the offspring. We investigated whether these effects may persist in subsequent generations.
Design  Historical cohort study.
Setting  Interview during a clinic or home visit or by telephone.
Population  Men and women born in the Wilhelmina Gasthuis in Amsterdam between November 1943 and February 1947.
Methods  We interviewed cohort members (F1) born around the time of the 1944–45 Dutch famine, who were exposed or unexposed to famine in utero , about their offspring (F2).
Main outcome measures  Birthweight, birth length, ponderal index and health in later life (as reported by F1) of the offspring (F2) of 855 participating cohort members, according to F1 famine exposure in utero .
Results  F1 famine exposure in utero did not affect F2 ( n = 1496) birthweight, but, among the offspring of famine-exposed F1 women, F2 birth length was decreased (−0.6 cm, P adjusted for F2 gender and birth order = 0.01) and F2 ponderal index was increased (+1.2 kg/m³, P adjusted for F2 gender and birth order = 0.001). The association remained unaltered after adjusting for possible confounders. The offspring of F1 women who were exposed to famine in utero also had poor health 1.8 (95% CI 1.1–2.7) times more frequently in later life (due to miscellaneous causes) than that of F1 unexposed women.
Conclusions  We did not find transgenerational effects of prenatal exposure to famine on birthweight nor on cardiovascular and metabolic disease rates. F1 famine exposure in utero was, however, associated with increased F2 neonatal adiposity and poor health in later life. Our findings may imply that the increase in chronic disease after famine exposure in utero is not limited to the F1 generation but persists in the F2 generation.     

Regulation of obesity and lipid disorders by herbal extracts from Morus alba, Melissa officinalis, and Artemisia capillaris in high-fat diet-induced obese mice

Melissa officinalis L. (Labiatae), Morus alba L. (Moraceae), and Artemisia capillaris Thunb. (Compositae) are suggested to be involved in the regulation of hyperlipidemia. We hypothesized that Ob-X, a mixture of three herbs, Morus alba, Melissa officinalis and Artemisia capillaris [corrected] improves lipid metabolism, body weight gain and adiposity and that peroxisome proliferator-activated receptor alpha (PPARalpha) is associated with these events. Mice fed a high-fat diet for 12 weeks exhibited increases in body weight gain and adipose tissue mass compared with mice fed a low fat diet. However, feeding a high-fat diet supplemented with Ob-X significantly reduced these effects. Ob-X treatment also decreased the circulating levels of triglycerides and total cholesterol, and inhibited hepatic lipid accumulation. Ob-X supplementation was found to increase the hepatic mRNA levels of PPARalpha target enzymes responsible for fatty acid beta-oxidation. Moreover, Ob-X elevated the endogenous expression of a luciferase reporter gene containing three copies of a PPAR response element (PPRE) in NMu2Li liver cells. These data demonstrate that Ob-X regulates body weight gain, adipose tissue mass, and lipid metabolism in part through changes in the expression of hepatic PPARalpha target genes.     

不同体脂含量儿童身体机能素质比较

目的 分析不同体脂含量儿童身体机能和运动素质的差异,为控制体成分、增强身体素质提供依据.方法 测量4 346名7～12岁儿童肱三头肌部和肩胛下角部皮褶厚度,推算体脂比(BF%),依据各年龄体脂比的第25和75百分位数,将受检儿童分为低体脂比组(BF%＜P25)、中体脂比组(P25≤BF%≤P75)、高体脂比组(BF%＞P75).分析3组儿童的身体机能和素质差异.结果 3组儿童身体机能和运动素质差异有统计学意义,肺活量、收缩压、舒张压和握力表现为高体脂比组＞中体脂比组＞低体脂比组,呈现随体脂比增长而梯次上升的趋势;肺活量/体重指数、速度(50 m跑)、立定跳远、力量(男斜身引体、女1 min仰卧起坐)和耐力跑(50 m×8往返跑)表现为低体脂比组＞中体脂比组＞高体脂比组,呈现随体脂比增长而梯次下降的趋势.结论 体脂含量过高对儿童身体素质有负面影响.应控制儿童体脂含量,增强身体素质.     

Is the control of fat ingestion sexually differentiated?

Sexual differentiation is a fundamental aspect of human physiology [Wizemann TM, Pardue M-L, editors. Exploring the biological contributions to human health: does sex matter? Washington DC, National Academy Press, 2001]. Therefore, this review considers whether the physiological control of eating, as related to dietary fat, is sexually differentiated. The effects of dietary fat are considered from the perspective of stimuli controlling eating that arise from oral, gastric, intestinal, hepatic, and adipose sites. The data reviewed provide substantial support for hypothesis that many such controls of fat ingestion are sexually differentiated in both humans and laboratory animals. Because as yet little is established definitively, however, the apparently most promising questions and methodologies for future work are emphasized.     

A prospective study of maternal prenatal weight and offspring cardiometabolic health in midchildhood

PurposeTo examine the relations of maternal prepregnancy body mass index (ppBMI) and gestational weight gain (GWG) with offspring cardiometabolic health.DesignWe studied 1090 mother–child pairs in Project Viva, a Boston-area prebirth cohort. We measured overall (dual x-ray absorptiometry total fat; body mass index z-score) and central adiposity (dual x-ray absorptiometry trunk fat), and systolic blood pressure in offspring at 6 to 10 years. Fasting bloods (n = 687) were assayed for insulin and glucose (for calculation of homeostatic model assessment of insulin resistance), triglycerides, leptin, adiponectin, high sensitivity C-reactive protein, and interleukin 6. Using multivariable linear regression, we examined differences in offspring outcomes per 1 SD maternal ppBMI and GWG.ResultsAfter adjustment for confounders, each 5 kg/m² higher ppBMI corresponded with 0.92 kg (95% confidence interval, 0.70–1.14) higher total fat, 0.27 BMI z-score (0.21–0.32), and 0.39 kg (0.29–0.49) trunk fat. ppBMI was also positively associated with homeostatic model assessment of insulin resistance, leptin, high sensitivity C-reactive protein, interleukin 6, and systolic blood pressure; and lower adiponectin. Each 5 kg of GWG predicted greater adiposity (0.33 kg [0.11–0.54] total fat; 0.14 kg [0.04–0.23] trunk fat) and higher leptin (6% [0%–13%]) in offspring after accounting for confounders and ppBMI.ConclusionsChildren born to heavier mothers have more overall and central fat and greater cardiometabolic risk. Offspring of women with higher GWG had greater adiposity and higher leptin.     

Anthropometric and Skin Fold Thickness Measurements of Newborns of Gestational Glucose Intolerant Mothers: Does it Indicate Disproportionate Fetal Growth?

Aim of the StudyStudies have shown that gestational diabetes mellitus (GDM) causes disproportionate growth and increased adiposity in their newborns; however, the effect of gestational glucose intolerance (GGI), i.e., 2 h plasma glucose (PG) between 120 and 139 mg/dl in pregnancy on their newborns growth and adiposity is not well established. The objective of the present study is to evaluate the effect of GGI in pregnancy on anthropometry and adiposity of their newborns at birth in urban South Indian population.Materials and MethodsAn observational study was conducted on 119 urban South Indian pregnant women and their newborns. PG levels 2 h after ingestion of 75 g glucose load were determined between 24 and 28 weeks of gestation, and depending on their PG levels, these women were categorized into three different groups, (a) normal glucose tolerance (NGT)-2 h PG < 120 mg/dl, (b) GGI-2 h PG between 120 and 139 mg/dl and (c) GDM-2 h PG > or = 140 mg/dl. GDM mothers were treated with insulin and MNT advised. GGI mothers were advised MNT. These women were followed up till delivery. After delivery, their newborn’s anthropometry like weight, length, head circumference (HC), chest circumference (CC), mid-arm circumference, abdominal circumference, bisacromial diameter and subscapular and triceps skin fold thicknesses (SFT) was measured within 72 h of birth. Effect of GGI in pregnancy on newborn’s anthropometry and SFT was analyzed and studied in comparison with newborns of other two categories. Further, the newborns were stratified into four groups according to their birth weight and newborns of GGI category were compared with newborns of other two categories of same weight.ResultsThe triceps and subscapular skin fold thicknesses which are direct measurements of adiposity were significantly higher in newborns of GGI mothers compared to newborns of GDM and NGT mothers. GGI category newborns showed increased adiposity even when they were compared with newborns of GDM and NGT category of same weight. Also measurements which are likely to increase due to increased adiposity like bisacromial diameter, abdominal circumference, mid-arm circumference were significantly higher in GGI category newborns. On the other hand, measurements which indicate skeletal growth like length, HC, CC were similar in all three category newborns. This confirmed disproportionate growth and increased adiposity in newborns of GGI mothers. It should be noted here that the GDM mothers were on MNT and treated with insulin, the dose of insulin was adjusted so as to mimick Fasting PG and Post Prandial PG levels of NGT mothers. ConclusionGestational glucose intolerance during pregnancy does cause disproportionate growth (increased fat body mass but not skeletal mass) and increased adiposity in their newborns. This emphasizes the need for strict glycemic control (2 h of PG level after 75 grams glucose load to < 120 mg/dl and PPPG levels to < 120 mg/dl) during pregnancy. Larger multicentered studies are recommended to confirm this association.     

Adiposity,body composition and ventricular–arterial stiffness in the elderly: the Atherosclerosis Risk in Communities Study

Aim

Weight gain appears to accelerate age‐related ventricular–arterial stiffening, which has been implicated in the development of heart failure (HF), but it is unclear whether body fat accumulation underpins this association. We evaluated the relationship of adiposity, using measures of body composition, with ventricular–arterial stiffness among the elderly in the community.

Methods and results

Adiposity was accessed through body mass index (BMI), waist circumference, and body fat percentage. We studied the association of these measures with carotid–femoral pulse wave velocity (cfPWV), arterial elastance index (EaI), left ventricular (LV) end‐systolic elastance index (EesI) and LV end‐diastolic elastance index (EedI) in 5520 community‐based, elderly Atherosclerosis Risk in Communities (ARIC) Study participants, who underwent echocardiography between 2011 and 2013. BMI and waist circumference were directly associated with EaI, EedI and EesI even after adjusting for age, sex, race, hypertension, diabetes mellitus, heart rate, prevalent coronary heart disease and HF. After further adjustment for BMI, body fat percentage demonstrated significant independent linear relationships with EaI [standardized beta coefficient (β)=0.17, P<0.001], EesI (β=0.08, P=0.003) and EedI (β=0.20, P<0.001), and significant non‐linear relationships with cfPWV (P=0.033).

Conclusion

In this biracial community‐based cohort, increased adiposity was associated with increased ventricular–arterial stiffness among the elderly and suggests a potential mechanism by which obesity might contribute to the development of HF.