A Model of Metabolic Syndrome and Related Diseases with Intestinal Endotoxemia in Rats Fed a High Fat and High Sucrose Diet

Aim

We sought develop and characterize a diet-induced model of metabolic syndrome and its related diseases.

Methods

The experimental animals (Spague-Dawley rats) were randomly divided into two groups, and each group was fed a different feed for 48 weeks as follows: 1) standard control diet (SC), and 2) a high sucrose and high fat diet (HSHF). The blood, small intestine, liver, pancreas, and adipose tissues were sampled for analysis and characterization.

Results

Typical metabolic syndrome (MS), non-alcoholic fatty liver disease (NAFLD), and type II diabetes (T2DM) were common in the HSHF group after a 48 week feeding period. The rats fed HSHF exhibited signs of obesity, dyslipidemia, hyperglycaemia, glucose intolerance, and insulin resistance (IR). At the same time, these animals had significantly increased levels of circulating LPS, TNFα, and IL-6 and increased ALP in their intestinal tissue homogenates. These animals also showed a significant reduction in the expression of occluding protein. The HSHF rats showed fatty degeneration, inflammation, fibrosis, cirrhosis, and lipid accumulation when their liver pathologies were examined. The HSHF rats also displayed increased islet diameters from 12 to 24 weeks, while reduced islet diameters occurred from 36 to 48 weeks with inflammatory cell infiltration and islet fat deposition. The morphometry of adipocytes in HSHF rats showed hypertrophy and inflammatory cell infiltration. HSHF CD68 analysis showed macrophage infiltration and significant increases in fat and pancreas size. HSHF Tunel analysis showed significant increases in liver and pancreas cell apoptosis.

Conclusions

This work demonstrated the following: 1) a characteristic rat model of metabolic syndrome (MS) can be induced by a high sucrose and high fat diet, 2) this model can be used to research metabolic syndrome and its related diseases, such as NAFLD and T2DM, and 3) intestinal endotoxemia (IETM) may play an important role in the pathogenesis of MS and related diseases, such as NAFLD and T2DM.     

Sex Hormones and Sexual Function in Obese Men Losing Weight

Objective: To study the impact of a weight‐loss program on sex hormones and sexual function among 38 middle‐aged obese men (BMI ≥35 kg/m²). Research Methods and Procedures: A randomized controlled clinical trial was conducted. The treatment group (n = 19) participated in a 4‐month weight‐loss program including 10 weeks on a very‐low‐energy diet (VLED) and 17 behavior modification visits. There was no intervention in the control group (n = 19). Both groups were followed for 8 months, i.e., 22 weeks after the active weight loss in the treatment group. The outcome measures (weight, sex hormones, sexual function, leptin, and metabolic variables) were obtained at baseline and at three time‐points during follow‐up. Results: The mean weight loss in the treatment group was 21 kg at the end of the 10‐week VLED. At the end of follow‐up, the maintained weight loss was 17 kg of baseline weight. The control group was weight stable throughout the study. In the treatment group, increases in sex hormone‐binding globulin, testosterone, and high‐density lipoprotein‐cholesterol, as well as decreases in insulin and leptin, were maintained until the end of follow‐up, although with VLED, the level of several hormones and metabolic variables improved transiently during the rapid weight loss. There were no significant changes in the questionnaire scores on sexual function in either group. Discussion: We conclude that obese men lose weight and increase their serum testosterone level on a weight‐loss program with VLED and behavior modification. However, they do not change their sexual function scores.     

Concentration and composition of serum lipoproteins during a low-fat diet at two levels of polyunsaturated fat

A 12-week dietary intervention was carried out among 40 families from North Karelia, a county in Finland with an exceptionally high rate of coronary heart disease and high serum cholesterol values. The proportion of dietary energy derived from fat was reduced during the 12-week intervention period from about 39% to 23% in all families. The families were randomly allocated into two groups. Twenty families consumed a diet with a polyunsaturated to saturated fat (P/S) ratio of 0.9 (group I), while the other 20 families had a diet with a P/S ratio of 0.4 (group II). Total serum cholesterol decreased by 16% and 9% in men of groups I and II, respectively, and by 16% in women of both groups. These changes were due to a decrease in both low density lipoprotein (LDL) and high density lipoprotein (HDL) cholesterol. LDL cholesterol and phospholipid reached minimum values after 6 weeks on both intervention diets, but LDL protein responded more slowly. Thus, after 6 weeks LDL had an altered composition containing less cholesterol and phospholipids and more protein and triglycerides than during the baseline diet. During the intervention, the linoleic acid content in the serum cholesteryl ester fraction increased, and the magnitude of this change correlated negatively with the changes in total and LDL cholesterol. The decrease in HDL cholesterol during the two intervention diets was due to a fall in the HDL2 cholesterol (29% and 24% in men, and 26% and 25% in women in groups I and II, respectively).(ABSTRACT TRUNCATED AT 250 WORDS)     

Variations in Body Composition and Plasma Lipids in Response to a High‐Carbohydrate Diet

Objective: To examine the extent to which variations in body composition modulate changes in the lipid profile in response to the ad libitum consumption of a diet rich in carbohydrates (CHOs) (high‐CHO diet: 58% of energy as CHOs) or high in fat and in monounsaturated fatty acids (MUFAs) (high‐MUFA diet: 40% of energy as fat, 23% as MUFAs). Research Methods and Procedures: Sixty‐three men were randomly assigned to one of the two diets that they consumed for 6 to 7 weeks. Body composition and fasting plasma lipid levels were measured at the beginning and the end of the dietary intervention. Results: The high‐CHO and high‐MUFA diets induced significant and comparable reductions in body weight and waist circumference. These changes were accompanied by significant and comparable (p < 0.01) reductions in total plasma cholesterol and low‐density lipoprotein cholesterol levels. However, the high‐MUFA diet had more beneficial effects on plasma triglyceride concentrations (p < 0.01) and on plasma high‐density lipoprotein cholesterol levels (p = 0.02) compared with the high‐CHO diet. Diet‐induced changes in waist circumference were significantly associated with changes in low‐density lipoprotein cholesterol levels in the high‐CHO group (r = 0.39, p = 0.03) but not in the high‐MUFA group (r = 0.16, p = 0.38). Discussion: Improvements in plasma lipids induced by the ad libitum consumption of a high‐CHO diet seem to be partly mediated by changes in body weight, whereas lipid changes induced by the high‐MUFA diet seem to be independent of changes in body weight.     

The Estrogen Antagonist EM‐652 and Dehydroepiandrosterone Prevent Diet‐ and Ovariectomy‐Induced Obesity

Objective: EM‐652 is a pure antiestrogen in human breast and uterine cancer cells that also reduces bone loss and plasma lipid levels in the rat. This study aimed to assess the ability of EM‐652, alone or with dehydroepiandrosterone (DHEA), to prevent obesity and related metabolic abnormalities induced by an obesity‐promoting diet and ovariectomy. Research Methods and Procedures: Female rats were fed a high‐sucrose, high‐fat (HSHF) diet, were left intact or ovariectomized (OVX), and were treated with EM‐652, DHEA, or both for 20 days. Variables of energy balance and determinants of lipid metabolism and insulin sensitivity were assessed. Results: The HSHF diet (vs. chow) and OVX both increased energy intake and gain, as well as energetic efficiency. Both EM‐652 and DHEA prevented diet‐ and OVX‐induced energy gain mainly by decreasing fat deposition, without being additive. The modest EM‐652‐induced increase in liver triglycerides of intact rats was prevented by its combination with DHEA. EM‐652, but not DHEA, decreased cholesterolemia. The HSHF diet and OVX reduced insulin sensitivity, an effect that was attenuated by EM‐652 and abrogated by DHEA and EM‐652+DHEA. Treatment with EM‐652, DHEA, or their combination abolished the diet‐ and OVX‐induced increase in adipose lipoprotein lipase activity that accompanied fat gain. Discussion: EM‐652 is an effective agent to prevent diet‐ and OVX‐induced obesity and its associated cardiovascular risk factors such as insulin resistance. The addition of DHEA prevents hepatic lipid accumulation and further ameliorates insulin sensitivity. The beneficial metabolic effects of such combined steroid therapy may, therefore, eventually prove to be clinically relevant.     

A Murine Model of Obesity With Accelerated Atherosclerosis

The epidemic of obesity sweeping developed nations is accompanied by an increase in atherosclerotic cardiovascular diseases. Dyslipidemia, diabetes, hypertension, and obesity are risk factors for cardiovascular disease. However, delineating the mechanism of obesity‐accelerated atherosclerosis has been hampered by a paucity of animal models. Similar to humans, apolipoprotein E–deficient (apoE^?/?) mice spontaneously develop atherosclerosis over their lifetime. To determine whether apoE^?/? mice would develop obesity with accelerated atherosclerosis, we fed mice diets containing 10 (low fat (LF)) or 60 (high fat (HF)) kcal % from fat for 17 weeks. Mice fed the HF diet had a marked increase in body weight and atherosclerotic lesion formation compared to mice fed the LF diet. There were no significant differences between groups in serum total cholesterol, triglycerides, or leptin concentrations. Plasma concentrations of the acute‐phase reactant serum amyloid A (SAA) are elevated in both obesity and cardiovascular disease. Accordingly, plasma SAA concentrations were increased fourfold (P < 0.01) in mice fed the HF diet. SAA was associated with both pro‐ and antiatherogenic lipoproteins in mice fed the HF diet compared to those fed the LF diet, in which SAA was primarily associated with the antiatherogenic lipoprotein high‐density lipoprotein (HDL). Moreover, SAA was localized with apoB‐containing lipoproteins and biglycan in the vascular wall. Taken together, these data suggest male apoE‐deficient mice are a model of metabolic syndrome and that chronic low level inflammation associated with increased SAA concentrations may mediate atherosclerotic lesion formation.     

Very low-carbohydrate versus isocaloric high-carbohydrate diet in dietary obese rats

Objective: The effects of a very low‐carbohydrate (VLC), high‐fat (HF) dietary regimen on metabolic syndrome were compared with those of an isocaloric high‐carbohydrate (HC), low‐fat (LF) regimen in dietary obese rats. Research Methods and Procedures: Male Sprague‐Dawley rats, made obese by 8 weeks ad libitum consumption of an HF diet, developed features of the metabolic syndrome vs. lean control (C) rats, including greater visceral, subcutaneous, and hepatic fat masses, elevated plasma cholesterol levels, impaired glucose tolerance, and fasting and post‐load insulin resistance. Half of the obese rats (VLC) were then fed a popular VLC‐HF diet (Weeks 9 and 10 at 5% and Weeks 11 to 14 at 15% carbohydrate), and one‐half (HC) were pair‐fed an HC‐LF diet (Weeks 9 to 14 at 60% carbohydrate). Results: Energy intakes of pair‐fed VLC and HC rats were less than C rats throughout Weeks 9 to 14. Compared with HC rats, VLC rats exhibited impaired insulin and glycemic responses to an intraperitoneal glucose load at Week 10 and lower plasma triacylglycerol levels but retarded loss of hepatic, retroperitoneal, and total body fat at Week 14. VLC, HC, and C rats no longer differed in body weight, plasma cholesterol, glucose tolerance, or fasting insulin resistance at Week 14. Progressive decreases in fasting insulin resistance in obese groups paralleled concomitant reductions in hepatic, retroperitoneal, and total body fat. Discussion: When energy intake was matched, the VLC‐HF diet provided no advantage in weight loss or in improving those components of the metabolic syndrome induced by dietary obesity and may delay loss of hepatic and visceral fat as compared with an HC‐LF diet.     

Transient Increase in HDL‐Cholesterol During Weight Gain by Hyperalimentation in Healthy Subjects

Determination of lipid levels is fundamental in cardiovascular risk assessment. We studied the short‐term effects of fast food‐based hyperalimentation on lipid levels in healthy subjects. Twelve healthy men and six healthy women with a mean age of 26 ± 6.6 years and an aged‐matched control group were recruited for this prospective interventional study. Subjects in the intervention group aimed for a body weight increase of 5–15% by doubling the baseline caloric intake by eating at least two fast food‐based meals a day in combination with adoption of a sedentary lifestyle for 4 weeks. This protocol induced a weight gain from 67.6 ± 9.1 kg to 74.0 ± 11 kg (P < 0.001). A numerical increase in the levels of high‐density lipoprotein (HDL)‐cholesterol occurred in all subjects during the study and this was apparent already at the first week in 16/18 subjects (mean increase at week 1: +22.0 ± 16%, range from ?7 to +50%), whereas the highest level of HDL during the study as compared with baseline values varied from +6% to +58% (mean +31.6 ± 15%). The intake of saturated fat in the early phase of the trial related positively with the HDL‐cholesterol‐increase in the second week (r = 0.53, P = 0.028). Although the levels of insulin doubled at week 2, the increase in low‐density lipoprotein (LDL)‐cholesterol was only +12 ± 17%, and there was no statistically significant changes in fasting serum triglycerides. We conclude that hyperalimentation can induce a fast but transient increase in HDL‐cholesterol that is of clinical interest when estimating cardiovascular risk based on serum lipid levels.     

高脂膳食对小鼠生化及病理形态的影响

目的高脂膳食对机体血液、组织匀浆中各种生化指标的影响,尤其是对胆固醇等脂质代谢的影响,为研究高胆固醇引起的心血管等疾病建立模型。方法将C57BL/6 j小鼠63只随机分为2组。普食组（用普通饲料饲喂）12只,雌雄各6只,高脂组（用高脂饲料饲喂）51只,雌26只、雄25只。单笼饲喂,饲喂期为67 d。观察动物体重、摄食量、比较血液以及肝、肾组织匀浆中有关脂类代谢和抗氧化方面的生化指标以及组织病理学观察。结果高脂组血液中胆固醇（TC）和低密度脂蛋白胆固醇（LDLC）均显著高于普食组（P〈0.05）;高脂组肝、肾脏组织匀浆中T-AOC、CuZn-SOD、SOD、AKP、NOS、MDA的水平与普食组相比均无统计学差异;与普食组相比,雄性小鼠摄食量差异显著（P〈0.05）、体重差异不显著;病理观察可见高脂组中肝细胞空泡变性。结论通过高脂膳食成功的建立了高胆固醇血症模型,该模型有可能在胆固醇浓度升高引起的脂质代谢异常、动脉粥样硬化、冠心病和其他代谢性疾病的研究中发挥作用。     

Treatment of Obese Adolescents: The Influence of Periodization Models and ACE Genotype

The aims of the present study were to compare the effects of two periodization models on metabolic syndrome risk factors in obese adolescents and verify whether the angiotensin‐converting enzyme (ACE) genotype is important in establishing these effects. A total of 32 postpuberty obese adolescents were submitted to aerobic training (AT) and resistance training (RT) for 14 weeks. The subjects were divided into linear periodization (LP, n = 16) or daily undulating periodization (DUP, n = 16). Body composition, visceral and subcutaneous fat, glycemia, insulinemia, homeostasis model assessment of insulin resistance (HOMA‐IR), lipid profiles, blood pressure, maximal oxygen consumption (VO_2max), resting metabolic rate (RMR), muscular endurance were analyzed at baseline and after intervention. Both groups demonstrated a significant reduction in body mass, BMI, body fat, visceral and subcutaneous fat, total and low‐density lipoprotein cholesterol, blood pressure and an increase in fat‐free mass, VO_2max, and muscular endurance. However, only DUP promoted a reduction in insulin concentrations and HOMA‐IR. It is important to emphasize that there was no statics difference between LP and DUP groups; however, it appears that there may be bigger changes in the DUP than LP group in some of the metabolic syndrome risk factors in obese adolescents with regard to the effect size (ES). Both periodization models presented a large effect on muscular endurance. Despite the limitation of sample size, our results suggested that the ACE genotype may influence the functional and metabolic characteristics of obese adolescents and may be considered in the future strategies for massive obesity control.     

Plasma Markers of Cholesterol Homeostasis and Apolipoprotein B‐100 Kinetics in the Metabolic Syndrome

Objective: The metabolic syndrome is characterized by defective hepatic apolipoprotein B‐100 (apoB) metabolism. Hepato‐intestinal cholesterol metabolism may contribute to this abnormality. Research Methods and Procedures: We examined the association of cholesterol absorption and synthesis with the kinetics of apoB in 35 obese subjects with the metabolic syndrome. Plasma ratios of campesterol and lathosterol to cholesterol were used to estimate cholesterol absorption and synthesis, respectively. Very‐low‐density lipoprotein (VLDL), intermediate‐density lipoprotein (IDL), and low‐density lipoprotein apoB kinetics were studied using stable isotopy and mass spectrometry. Kinetic parameters were derived using multicompartmental modeling. Results: Compared with controls, the obese subjects had significantly lower plasma ratios of campesterol, but higher plasma ratios of lathosterol (p < 0.05 in both). This was associated with elevated VLDL‐apoB secretion rate (p < 0.05) and delayed fractional catabolism of IDL and low‐density lipoprotein‐apoB (p < 0.01). In the obese group, plasma ratios of campesterol correlated inversely with VLDL‐apoB secretion (r = ?0.359, p < 0.05), VLDL‐apoB (r = ?0.513, p < 0.01) and IDL‐apoB (r = ?0.511, p < 0.01) pool size, and plasma lathosterol ratio (r = ?0.366, p < 0.05). Subjects with low cholesterol absorption had significantly higher VLDL‐apoB secretion, VLDL‐apoB and IDL‐apoB pool size, and plasma lathosterol ratio (p < 0.05 in both) than those with high cholesterol absorption. Discussion: Subjects with the metabolic syndrome have oversecretion of VLDL‐apoB and decreased catabolism of apoB‐containing particles and low absorption and high synthesis rates of cholesterol. These changes in cholesterol homeostasis may contribute to the kinetic defects in apoB metabolism in the metabolic syndrome.     

Metabolic Syndrome and Changes in Body Fat From a Low‐fat Diet and/or Exercise Randomized Controlled Trial

It is difficult to identify the successful component(s) related to changes in metabolic syndrome (MetS) from lifestyle interventions: the weight loss, the behavior change, or the combination. The purpose of this study is to determine the effects of a weight‐stable randomized controlled trial of low‐fat diet and exercise, alone and in combination, on MetS. Men (n = 179) and postmenopausal women (n = 149) with elevated low‐density lipoprotein cholesterol (LDL‐C) and low high‐density lipoprotein cholesterol (HDL‐C) were randomized into a 1‐year, weight‐stable trial with four treatment groups: control (C), diet (D), exercise (E), or diet plus exercise (D+E). MetS was defined using a continuous score. Changes in MetS score (ΔMetS) were compared between groups using analysis of covariance, stratified by gender and using two models, with and without baseline and change in percent body fat (ΔBF) as a covariate. In men, ΔMetS was higher for D vs. C (P = 0.04), D+E vs. C (P = 0.0002), and D+E vs. E (P = 0.02). For women, ΔMetS was greater for D vs. C (P = 0.045), E vs. C (P = 0.02), and D+E vs. C (P = 0.004). After adjusting for ΔBF, all differences between groups were attenuated and no longer significant. ΔMetS were associated with ΔBF for both men (P < 0.0001) and women (P = 0.004). After adjustment for ΔBF, low‐fat diet alone and in combination with exercise had no effect on MetS. The key component for MetS from low‐fat diet and/or increased physical activity appears to be body fat loss.     

Effects of dietary lactose on long-term high-fat-diet-induced obesity in rats

Objective: In this study, we examined the effects of lactose on long‐term high‐fat‐diet‐induced obesity in rats. Research Methods and Procedures: A total of 112 Sprague‐Dawley strain female rats (6 weeks old) were divided into four groups: a basic control diet group (Cont), 10% lactose diet group (Lac), high‐fat diet group (Fat), and high‐fat with 10% lactose diet group (Fat+Lac). After 0, 7, 14, and 84 days from starting the experimental diet, the animals were fasted overnight and killed by bleeding from the abdominal aorta under anesthesia (n = 8 or 9/group). Results: After 84 days, the addition of lactose to the high‐fat diet decreased the final body weight, body weight gain, fat accumulation, and the levels of serum leptin, serum triglycerides, and serum glucose significantly (p < 0.05). Although there was no significant difference in the levels of serum calcium and phosphorus between the Fat and Fat+Lac groups, lumbar vertebral bone mineral density was significantly higher in the Fat+Lac group than in the Cont group on Day 82. Interestingly, the level of serum 1α, 25‐dihydroxyvitamin D₃ in the Fat+Lac group on Day 84 was reduced by 74% compared with the Fat group (p < 0.01), while there was no significant difference in serum parathyroid hormone levels between the Fat and Fat+Lac groups. Discussion: This is the first study to suggest that the addition of lactose to a long‐term high‐fat diet may regulate not only calcium metabolism but also fat deposition. Further studies on the mechanism of dietary lactose in the regulation of adiposity would provide valuable data for the prevention of long‐term high‐fat‐diet‐induced obesity.     

Lipoprotein profiles and glucose tolerance in lean and obese chimpanzees

Abstract: We compared serum lipid profiles and glucose tolerance of obese and lean chimpanzees maintained on a 10.9% fat diet. Seven of 14 obese and 6 of 17 lean chimpanzees were hypercholesterolemic (low density lipoprotein cholesterol > 160 mg/dl), three obese and three lean animals had total cholesterol/high density lipoprotein cholesterol ratios of 5.9–10.7, and two obese and one lean chimpanzee had abnormal glucose tolerance. Useful numbers of captive chimpanzees thus exhibit metabolic abnormalities without recourse to high fat diets and could serve as surrogates in studies of human metabolic diseases.     

三种金花茶提取物降脂作用实验研究

目的:探讨金花茶浓缩液、金花茶乙酸乙酯/二氯甲烷提取物以及金花茶水提物对高脂血症小鼠血脂的调节作用。方法:将小鼠按照体重随机分成正常饮食组和高脂饮食组,分别给予正常饲料和高脂饲料喂食,4周后将高脂饮食小鼠按照体重以及血脂水平(TC)随机分成金花茶浓缩液组、金花茶乙酸乙酯/二氯甲烷提取物组、金花茶水提物组以及辛伐他丁组。3种金花茶提取物以及辛伐他丁混悬液连续灌胃10周,同时给予高脂饮食。末次给药后禁食不禁水12 h,摘眼球取血,检测血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)、低密度脂蛋白(LDL-C)、谷丙转氨酶(ALT)、谷草转氨酶(AST)、超氧化物歧化酶(SOD)以及丙二醛(MDA)。结果:与模型组相比,金花茶浓缩液和辛伐他丁能显著降低血清TC、TG、LDL-C水平(P0.01或P0.05),但是对HDL-C无明显调节作用;对血清中的AST、ALT、SOD以及MDA影响不大。金花茶乙酸乙酯/二氯甲烷提取物以及水体物对血清中的TC、TG、LDL-C、HDL-C、AST、ALT、SOD及MDA无明显的调节作用。结论:金花茶浓缩液对高脂血症小鼠的血脂具有良好的调节作用。     

A randomized clinical trial testing treatment preference and two dietary options in behavioral weight management: preliminary results of the impact of diet at 6 months--PREFER study

Objective: The PREFER study objectives were to examine potential differences in weight loss during a standard behavioral intervention between subjects assigned to one of two calorie‐ and fat‐restricted diets [standard behavior treatment (SBT) and lacto‐ovo‐vegetarian ([SBT+LOV)], with or without regard to their preferred dietary treatment. This article reports the differences in outcomes between diet groups after the first 6 months of the intervention. Research Methods and Procedures: The study used a four‐group design. Subjects (n = 182) were randomized to a treatment preference group and then to a dietary treatment group. For this report, preference groups were combined to permit comparisons by dietary treatment only (SBT, n = 98; SBT+LOV, n = 84). Additional analyses compared SBT+LOV subjects who were 100% adherent (did not consume any meat, fish, or poultry, n = 47) to those who were <100% adherent (n = 24). Results: Significant differences were seen in the baseline to 6‐month change scores between the two groups for carbohydrate consumption (p = 0.013), protein consumption (p < 0.001), polyunsaturated‐to‐saturated fat ratio (p = 0.009), and low‐density lipoprotein‐cholesterol (LDL‐C) level (p = 0.013). Among SBT+LOV subjects, those who were 100% adherent experienced greater reductions in weight (p < 0.001), total cholesterol (p = 0.026), LDL‐C (p = 0.034), and glucose (p = 0.002) and consumed less fat (p = 0.030) compared with those who were <100% adherent. Discussion: Differences between dietary treatment groups at 6 months were minimal, most likely because one‐third of the SBT+LOV group did not follow the vegetarian diet and because both groups had the same calorie and fat restrictions. SBT+LOV subjects who were 100% adherent were more successful at both weight loss and cholesterol reduction than those who were <100% adherent, suggesting that vegetarian diets are efficacious for weight and cholesterol control.     

Defining Health‐Related Obesity in Prepubertal Children

Objective: The purpose of this study was to develop percentage of fat and waist circumference cut‐points in prepubertal children with the intention of defining obesity associated with cardiovascular disease (CVD) risk. Research Methods and Procedures: A cross‐sectional analysis of 87 prepubertal children aged 4 to 11 years was used. Percentage of body fat was determined by DXA. Waist circumference was measured to the nearest millimeter. Receiver Operating Characteristic analyses of percentage of fat and waist circumference were used to develop cut‐points for individuals with adverse levels of CVD risk factors. Results: The risk factors selected for analyses (i.e., fasting insulin, high‐density lipoprotein cholesterol, low‐density lipoprotein cholesterol, triglycerides, and total cholesterol/high‐density lipoprotein cholesterol) were significantly related to percentage of body fat and waist circumference. Likelihood ratios were used to identify percentage of fat and waist circumference cut‐points associated with adverse cardiovascular risk profiles. Two cut‐points, an upper cut‐point of 33% body fat and a lower cut‐point of 20% body fat, were derived. Waist circumference cut‐points indicative of adverse and normal risk‐factor profiles were 71 cm and 61 cm, respectively. Discussion: The data indicate that children with ≥33% body fat and children with a waist circumference ≥71 cm were more likely to possess an adverse CVD risk‐factor profile than a normal risk‐factor profile. The likelihood of children with <20% body fat or a waist circumference <61 cm possessing an adverse CVD risk‐factor profile as opposed to a normal risk‐factor profile was small. The cut‐points describe an adequate health‐related definition of childhood obesity.     

Comparison of the Relative Contributions of Intra‐Abdominal and Liver Fat to Components of the Metabolic Syndrome

Abdominally obese individuals with the metabolic syndrome often have excess fat deposition both intra‐abdominally (IA) and in the liver, but the relative contribution of these two deposits to variation in components of the metabolic syndrome remains unclear. We determined the mutually independent quantitative contributions of IA and liver fat to components of the syndrome, fasting serum (fS) insulin, and liver enzymes and measures of hepatic insulin sensitivity in 356 subjects (mean age 42 years, mean BMI 29.7 kg/m²) in whom liver fat and abdominal fat volumes were measured. IA and liver fat contents were correlated (r = 0.65, P < 0.0001). In multivariate linear regression analyses including either liver or IA fat, liver fat or IA fat explained variation in fS‐triglyceride (TG) and high‐density lipoprotein (HDL) cholesterol, plasma glucose, insulin and liver enzyme concentrations, and hepatic insulin sensitivity independent of age, gender, subcutaneous (SC) fat, and/or lean body mass (LBM). Including both liver and IA fat, liver and IA fat both explained variation in TG, HDL cholesterol, insulin and hepatic insulin sensitivity independent of each other and of age, gender, SC fat, and LBM. Liver fat independently predicted glucose and liver enzymes. SC fat and age explained variation in blood pressure. In conclusion, both IA and liver fat independently of each other explain variation in serum TG, HDL cholesterol, insulin concentrations and hepatic insulin sensitivity, thus supporting that both fat depots are important predictors of these components of the metabolic syndrome.     

Characterization and heritability of obesity and associated risk factors in vervet monkeys

Objective: The objective was to determine the prevalence and heritability of obesity and risk factors associated with metabolic syndrome (MS) in a pedigreed colony of vervet monkeys. Design: A cross‐sectional study of plasma lipid and lipoprotein concentrations, glycemic indices, and morphometric measures with heritability calculated from pedigree analysis. A selected population of females was additionally assessed for insulin sensitivity and glucose tolerance. Subjects: All mature male (n = 98), pregnant (n = 40) and non‐pregnant female (n = 157) vervet monkeys were included in the study. Seven non‐pregnant females were selected on the basis of high or average glycated hemoglobin (GHb) for further characterization of carbohydrate metabolism. Measurements: Morphometric measurements included body weight, length, waist circumference, and calculated BMI. Plasma lipids [total cholesterol (TC), triglycerides (TG), high‐density lipoprotein cholesterol (HDL‐C)] and glycemic measures (fasting blood glucose, insulin, and GHb) were measured. A homeostasis model assessment index was further reported. Glucose tolerance testing and hyperinsulinemic‐euglycemic clamps were performed on 7 selected females. Conclusion: Vervet monkeys demonstrate obesity, insulin resistance, and associated changes in plasma lipids even while consuming a low‐fat (chow) diet. Furthermore, these parameters are heritable. Females are at particular risk for central obesity and an unfavorable lipid profile (higher TG, TC, and no estrogen‐related increase in HDL‐C). Selection of females by elevated GHb indicated impaired glucose tolerance and was associated with central obesity. This colony provides a unique opportunity to study the development of obesity‐related disorders, including both genetic and environmental influences, across all life stages.