骨钙素与体脂及糖脂代谢的研究进展

骨钙素是由成骨细胞特异性分泌的非胶原蛋白,近年研究发现骨钙素不仅参与骨代谢,而且参与能量的调节,与糖脂代谢密切相关.深入研究骨钙素的生物学意义可能为肥胖、糖尿病和代谢综合征的防治提供新的靶点.     

Adiponectin relationship with lipid metabolism is independent of body fat mass: evidence from both cross-sectional and intervention studies

Adiponectin influences insulin sensitivity and lipid metabolism, but it is not clear whether these effects are correlated with fat mass or distribution. We studied the relationship between plasma adiponectin and leptin levels, insulin sensitivity, and serum lipids by a cross-sectional study (n = 242 subjects) and by an intervention study (95 of 242) to evaluate the effect of weight loss (WL). Considering all subjects both together and subdivided into nonobese (n = 107) and obese (n = 135) groups, plasma adiponectin, but not plasma leptin, was significantly (P < 0.01) correlated with insulin sensitivity [homeostasis model assessment of insulin-resistance index (HOMAIR), insulin sensitivity index (ISI) at oral glucose tolerance test, and clamp in 115 of 242 individuals], high-density lipoprotein cholesterol, and triglycerides. These relationships were still significant (P < 0.01) after adjusting for age, gender, body mass index (BMI), and ISI. After WL (-16.8 +/- 0.8%), plasma adiponectin increased, and plasma leptin decreased (P < 0.0001 for both). Their changes (Delta) were significantly correlated with Delta-BMI (P < 0.05 for both). Delta-Adiponectin, but not Delta-leptin, significantly (P < 0.001) correlated with Delta-high-density lipoprotein cholesterol and Delta-triglycerides; these correlations were independent of age, gender, Delta-BMI, and Delta-ISI (P < 0.005). In conclusion, both cross-sectional and intervention studies indicate that plasma adiponectin level correlates with serum lipids independently of fat mass. The intervention study also suggests that adiponectin increase after WL is correlated with serum lipid improvement independently of insulin sensitivity changes.     

Obesity and serum lipids: an evaluation of the relative contribution of body fat and fat distribution to lipid levels

The association of obesity and hyperlipidemia does not mean that fatness per se is the primary determinant of the lipid abnormality. To evaluate the contribution of fatness to fasting levels of serum triglycerides (TG), LDL cholesterol (LDL-C), and HDL cholesterol (HDL-C), we analyzed data on 368 caucasian adults (286 women, 82 men) consecutively entering a weight control program. Although most subjects were overweight, the population represented a wide spectrum of body weights and lipid levels. Study variables included body fat mass (by total body water), fat free mass (FFM), body build (chest to height ratio), fat cell size and number (from bilateral buttock biopsy specimens), upper-lower body fat pattern by arm to thigh circumference ratio, central-peripheral fat pattern by subcapsular to triceps skinfold ratio, waist to hip ratio, and the presence or absence of diabetes. Our results concurred with previously noted correlations of body weight with TG (r = 0.29, P less than 0.0001) and with HDL-C (r = -0.28, P less than 0.0001) at least in the larger sample of women, but there was no significant correlation with LDL-C (r = -0.06). In order to evaluate the relative contribution of the various components of body composition and fat distribution to lipid levels, stepwise regression analyses were performed on the subgroups of women and men. Among women: TG level was predicted best by FFM, upper body fat pattern, age, and diabetes (explaining 30 percent of TG variance); LDL-C level was predicted by age only (explaining 12 percent of variance); and HDL-C level was predicted by body build only (8 percent). Among men: TG level was predicted best by central and upper body fat patterns and diabetes (31 percent of variance); LDL-C and HDL-C levels were not significantly predicted by any of the 11 study variables. These results, obtained from cross-sectional analysis of a predominantly obese sample, suggest that lipid levels may be more directly related to body fat pattern, fat free mass and body build than to body fatness itself.     

Dietary lipids,gut microbiota and lipid metabolism

Reviews in Endocrine and Metabolic Disorders - The gut microbiota is a central regulator of host metabolism. The composition and function of the gut microbiota is dynamic and affected by diet...     

Plasma oestrone-fatty acid ester levels are correlated with body fat mass in humans

OBJECTIVE: The metabolites of steroidal hormones, including sulphate, glucuronide, and fatty acid (FA) ester derivatives, have received little attention, although these steroid derivatives are essential components in the global assessment of steroid metabolism. The study of FA-derivatives could, in obesity, contribute some insights into factors modulating steroid metabolism and their plasma levels. In a recent study we found that, in rats, an oestrone-fatty acid ester (E1-FA) was produced by white adipose tissue and released into lipoproteins in the blood-stream. We have examined whether E1-FA levels correlate with body fat and insulin sensitivity in humans. SUBJECTS: A sample of 20 men and 22 women with varying levels of total body fat (mean body mass index (BMI) 29.2 +/- 4.7, range 22.2-35.8 in men; mean BMI 27.6 +/- 6.3, range 16.8-37.9 in women). All participants were healthy. MEASUREMENTS: We measured oestrone fatty acid esters (E1-FA), body fatness, and body fat distribution variables, as well as insulin sensitivity through a frequently sampled intravenous glucose tolerance test. Plasma E1-FA and serum leptin levels were measured by radioimmunoassay. RESULTS: E1-FA levels strongly correlated with BMI (r = 0.69, P = 0.001 in men; r = 0.75, P < 0.0001, in women) percent body fat (PBF, r = 0.52. P = 0.018 in men; and r = 0.69, P < 0.0001, in women) and with the sum of 4 fat skinfolds (sigma skinfolds). E1-FA level was significantly and positively associated with fasting insulin (r = 0.62, P = 0.003 in men, and r = 0.48, P = 0.023 in women) but not with fasting glucose levels. E1-FA correlated with insulin sensitivity (SI, r = -0.72 in men; and -0.76, in women, both P < 0.0001). In men, E1-FA levels also correlated with systolic blood pressure (r = 0.59, P = 0.01), total triglycerides (r = 0.63, P = 0.003), VLDL-triglycerides (r = 0.62, P = 0.004) and VLDL-cholesterol (r = 0.48, P = 0.03), but not with diastolic blood pressure, serum total or LDL-cholesterol, or total and HDL2 and HDL3 subfractions of HDL cholesterol. After controlling for fat mass, only the correlation between VLDL-triglycerides and E1-FA levels remained significant. In women, E1-FA levels correlated with total triglycerides (r = 0.66, P = 0.001), VLDL-triglycerides (r = 0.65, P = 0.001), VLDL-cholesterol (r = 0.63, P = 0.002), LDL-cholesterol (r = 0.57, P = 0.005) and total and HDL2 and HDL3 subfractions of HDL cholesterol (r = -0.58, -0.48, -0.61, P = 0.004, 0.02 and 0.002, respectively), but not with systolic or diastolic blood pressure or total cholesterol. However, covariance analysis revealed that controlling for the concomitant variation in body fat mass eliminated all these associations. Fasting plasma E1-FA concentration correlated with serum leptin (r = 0.60, P = 0.005 in men; r = 0.75, P = 0.0001, in women). However, these correlations no longer persisted after controlling for fat mass (r = 0.33 and 0.36, P = NS). Stepwise regression analysis models were tested, with E1-FA as the dependent variable, and sigma skinfolds and SI as independent covariables. Both the sigma skinfolds (P = 0.03) and SI (P = 0.01) entered the equation at a statistically significant level in men. Therefore, insulin sensitivity was related to E1-FA independently of fat in men. In women only sigma skinfolds (P = 0.04) entered the regression model at a statistically significantly level. Fifty-seven percent of the variance in plasma E1-FA levels in men, and 50% in women, was accounted for using a regression model that combined these variables. CONCLUSIONS: Oestrone-fatty acid esters circulate in human blood in proportion to body fat, independently of gender. Plasma oestrone-fatty acid ester levels are associated with insulin sensitivity in men, independently of body fat. These findings may widen our perspective on the regulation of insulin action and control of body weight.     

Sequential changes in lipid metabolism and the fatty acid profile in liver lipids during fasting and sepsis

The sequential changes in lipid metabolism and in the fatty acid profile of liver lipids during fasting and sepsis were studied. Liver and blood specimens were taken from normally fed rats and from nonseptically and septically fasted rats at 5, 24, and 48 hr. Sepsis was induced by injecting live Escherichia coli bacteria intraperitoneally. Sepsis attenuated the fasting-induced increase in beta-hydroxybutyrate and reduced liver and serum triglycerides at 5 hr. There was a percentage decline in the most abundant fatty acids in neutral lipids, namely oleic (18:1w9) and linoleic (18:2w6) acids. This was seen throughout fasting and septic fasting. These results indicate that 18:1w9 and 18:2w6 are used as energy substrates and are oxidized to beta-hydroxybutyrate during fasting and mainly to carbon dioxide during septic fasting. On the contrary, the most abundant fatty acids in phospholipids, stearic (18:0), arachidonic (20:4w6), and docosahexaenoic (22:6w3) acids, accumulated in neutral lipids and in phospholipids throughout fasting. However, during sepsis this accumulation was reduced in neutral lipids and reversed to a level below that in the fed and fasted state in phospholipids. These results indicate that a disturbance in membrane integrity and function induced by septic fasting may have pathophysiological consequences for lipid metabolism and liver function during sepsis.     

Relationship between body fat distribution and blood lipids in obese adolescents

Associations between body fat distribution, measured by waist/hip circumference ratio (WHR), and plasma lipids and lipoproteins were examined in 74 grossly obese adolescents. WHR was positively correlated in adolescent girls with total triglycerides (r = 0.44, P less than 0.01), total cholesterol (r = 0.49, P less than 0.001), and LDL-cholesterol (r = 0.59, P less than 0.001). In adolescent boys no correlation was found for total cholesterol but there were correlations for triglycerides (r = 0.41, P less than 0.05), LDL-cholesterol (r = 0.49, P less than 0.001), HDL-cholesterol (r = -0.66, P less than 0.001) and the ratio cholesterol/HDL-cholesterol (r = 0.62, P less than 0.001). Waist/hip ratio was not correlated with BMI or percentual overweight in obese girls, but a significant association was found in obese boys for both (r = -0.46, P less than 0.03 and r = 0.53, P less than 0.02). These results indicate that in obese girls a prevalence of abdominal fat distribution is correlated with increased triglycerides, serum cholesterol and LDL-C. In male adolescents total cholesterol is only slightly influenced but HDL-C concentrations are lower and LDL-C and the ratio CHOL/HDL-C higher.     

Effect of DL-alpha-lipoic acid on the status of lipid peroxidation and lipids in aged rats

The effect of dextro and levo (DL)-alpha-lipoic acid on lipid peroxidation and lipids has been evaluated in plasma, liver, and kidney of young and aged rats. The levels of thiobarbituric acid reactive substances (TBARS) and lipids were considerably higher in aged rats compared with younger controls. DL-alpha-lipoic acid (100 mg/kg body wt/day) was administered intraperitoneally for 7 and 14 days. Supplementation of lipoic acid in aged rats prevents the elevated levels of TBARS and lipids. From our observations, we conclude that lipoic acid is very effective in normalizing age-related alterations in lipids, and it can be implemented in the aged to minimize age-associated disorders where free radicals are the major cause.     

Bariatric surgery in obesity: changes of glucose and lipid metabolism correlate with changes of fat mass

Background and AimBariatric surgery induces significant weight loss and improves glucose metabolism in obese patients (BMI > 35 kg/m²). Our aim was to compare restrictive (LAGB, laparoscopic gastric banding) and malabsorptive approaches (BIBP, biliary-intestinal bypass) on the loss of fat-free mass (FFM), fat mass (FM), and on changes of glucose and lipid metabolism.Methods and ResultsBody composition (bio-impedance analysis, BIA), blood glucose (BG), insulin, triglycerides, total- and HDL-cholesterol, liver enzymes (AST and ALT) were measured at baseline and 1 year after surgery in patients undergoing LAGB, BIBP, and in diet-treated control patients. In the main study, with patients matched for initial BMI (43–55 kg/m², LAGB = 24, BIBP = 12, controls = 6), decreases of BMI, FM, BG and cholesterol were greater in patients with BIBP than with LAGB (p < 0.01), while decreases of FFM, insulin, HOMA-IR and triglycerides were similar. No effects on BMI, FM, FFM, BG, insulin, HOMA-IR or cholesterol were observed in the control patients. Decreases of BG, insulin, HOMA-IR, cholesterol and triglycerides correlated with FM but not with FFM decrease. Similar results were obtained in an additional study in patients with a different initial BMI (LAGB = 25, BIBP = 6, controls = 24) and when considering all subjects together. A decrease of liver enzymes (ALT) was greater with LAGB than with BIBP, and HDL-cholesterol increased with LAGB and decreased with BIBP.ConclusionBMI, FM, BG and cholesterol decrease more with malabsorptive than with restrictive surgery, while FFM, insulin, HOMA-IR and triglycerides decrease in a similar way. FFM loss is of low entity. Changes of glucose and lipid metabolism are proportional to a decrease of fat mass but not of fat-free mass.     

Administration of myostatin does not alter fat mass in adult mice

Aim:   Myostatin, a member of the TGF-beta superfamily, is produced by skeletal muscle and acts as a negative regulator of muscle mass. It has also been suggested that low-dose administration of myostatin (2 μg/day) in rodents can reduce fat mass without altering muscle mass. In the current study, we attempted to further explore the effects of myostatin on adipocytes and its potential to reduce fat mass, since myostatin administration could potentially be a useful strategy to treat obesity and its complications in humans.
Methods:   Purified myostatin protein was examined for its effects on adipogenesis and lipolysis in differentiated 3T3-L1 adipocytes as well as for effects on fat mass in wild-type, myostatin null and obese mice.
Results:   While myostatin was capable of inhibiting adipogenesis in 3T3-L1 cells, it did not alter lipolysis in fully differentiated adipocytes. Importantly, pharmacological administration of myostatin over a range of doses (2–120 μg/day) did not affect fat mass in wild-type or genetically obese (ob/ob, db/db) mice, although muscle mass was significantly reduced at the highest myostatin dose.
Conclusions:   Our results suggest that myostatin does not reduce adipose stores in adult animals. Contrary to prior indications, pharmacological administration of myostatin does not appear to be an effective strategy to treat obesity in vivo .     

Plasma lipids and apoproteins, body fat distribution and body fatness in early pubertal children

Besides body fatness, the body fat distribution is associated with coronary risk in adults, but little has been reported on this aspect in children. This study describes body fatness, body fat distribution (waist-to-hip ratio, WHR) and the plasma lipid and apoprotein profile (TC, HDL-C, LDL-C, TG, apo A-I and apo B) in 60 boys (age 10.8 +/- 0.1 year; mean +/- s.e.m.) and 64 girls (age 10.2 +/- 0.1 year), all caucasian. To avoid interference by the large changes in plasma sex hormone levels during puberty, only pre- and early pubertal children (Tanner stages of genital c.q. breast development 1 or 2) participated. Physical and sports activity was scored in hours per week using a questionnaire. The boys were taller than the girls (146.2 +/- 0.7 vs 143.2 +/- 0.9 cm; ANOVA, P less than or equal to 0.05) and their WHR was larger (0.88 +/- 0.01 vs 0.83 +/- 0.01; ANOVA, P less than or equal to 0.05). The boys spent 8.0 +/- 0.4 hours weekly on physical and sports activities, the girls 5.5 +/- 0.3 (ANOVA, P less than or equal to 0.05). The plasma lipid and apoprotein profiles were similar in both groups. Body fatness was significantly associated with the lipid and apoprotein profile, although in different ways in boys and girls. In boys there was a relationship with TG (r = 0.49), with apo B (r = 0.33) and with the apo A-I to apo B ratio (r = -0.24); in girls with TG (r = 0.25), HDL-C (r = -0.39), apo A-I (r = -0.28) and with the HDL-C to TC ratio (r = -0.31); P less than 0.05 for all correlations. A regional component of the subcutaneous fatmass, assessed by the partial correlations of the individual skinfold thicknesses with the plasma lipid and apoprotein profile after controlling for body fatness, was lacking in these early and prepubertal children. The WHR was associated with TC (r = 0.35), LDL-C (r = 0.32), apo B (r = 0.36) and with apo A-I/apo B (r = -0.34) in the girls after controlling for body fatness. Although closer investigation into the validity of the WHR as a measure of fat distribution in children is needed, the tentative conclusion is that in pre- and early pubertal girls the WHR has an impact on the plasma lipid and apoprotein profile similar to that seen in adults. It is suggested that in boys these relationships develop later in puberty.     

男性体脂肪含量及其分布与血脂关系的研究

目的探讨男性体脂肪含量及脂肪分布与血脂代谢的关系。方法采用临床横断面研究,对194例青岛港男职工行体脂肪测定仪检查和血脂的测定,将所有入选对象分为血脂异常组和血脂正常组,两组之间比较。结果两组间脂肪量和肥胖度差异没有统计学意义(P>0.05);血脂异常组脂肪率、腹部总脂肪面积、腰围(WC)、腰臀比(WHR)和体重高于对照组(P<0.05);脂肪量和肥胖度与甘油三酯(TG)成正相关;腹部总脂肪面积、WC和WHR均与总胆固醇(TC)、低密度脂蛋白-胆固醇(LDL-C)和TG成正相关,与高密度脂蛋白-胆固醇(HDL-C)成负相关;脂肪率与TC、LDL-C成正相关,与HDL-C成负相关。结论男性脂肪量、尤其是脂肪分布与血脂代谢有关,腹部总脂肪面积是预测心血管危险因素的一个指标。     

Possible role of adiponectin and insulin sensitivity in mediating the favorable effects of lower body fat mass on blood lipids

AIMS: The objective of this study was to investigate the role of insulin sensitivity and serum adiponectin concentration as determinants, in middle-aged men, of the relationship between lower body fat and blood lipids after truncal fat has been accounted for. METHODS: Men (443) aged 39-65 yr, body mass index 18-43 kg/m(2), participated in the study. The following variables were measured: regional body fat distribution as assessed by dual-energy x-ray absorptiometry, maximal oxygen uptake, physical activity, fasting levels of serum adiponectin, triglycerides, and high-density lipoprotein- and total cholesterol. Plasma glucose and serum insulin were measured in the fasting state and after an oral glucose load. RESULTS: Lower body fat mass was inversely associated with serum triglycerides and total cholesterol and positively with serum high-density lipoprotein-cholesterol after adjustment for age, lean tissue mass, truncal fat mass, weight history, maximal oxygen uptake, and the level of physical activity (P < 0.0005). Serum adiponectin level and Matsudas insulin sensitivity index were positively intercorrelated, and both were positively correlated to lower body fat mass. When including adiponectin and insulin sensitivity in the analyses, the relationships between lower body fat mass and serum lipids were partly explained. CONCLUSION: For a given level of truncal fat mass, a large lower body fat mass is associated with an advantageous blood lipid profile, which may be partially mediated by the relationships to both insulin sensitivity and serum adiponectin level.     

Metabolic adaptations in the adipose tissue that underlie the body fat mass gain in middle-aged rats

Little is known about adipocyte metabolism during aging process and whether this can influence body fat redistribution and systemic metabolism. To better understand this phenomenon, two animal groups were studied: young—14 weeks old—and middle-aged—16 months old. Periepididymal (PE) and subcutaneous (SC) adipocytes were isolated and tested for their capacities to perform lipolysis and to incorporate D-[U-¹⁴C]-glucose, D-[U-¹⁴C]-lactate, and [9,10(n)-³H]-oleic acid into lipids. Additionally, the morphometric characteristics of the adipose tissues, glucose tolerance tests, and biochemical determinations (fasting glucose, triglycerides, insulin) in blood were performed. The middle-aged rats showed adipocyte (PE and SC) hypertrophy and glucose intolerance, although there were no significant changes in fasting glycemia and insulin. Furthermore, PE tissue revealed elevated rates (+50 %) of lipolysis during beta-adrenergic-stimulation. There was also an increase (+62 %) in the baseline rate of glucose incorporation into lipids in the PE adipocytes, while these PE cells were almost unresponsive to insulin stimulation and less responsive (a 34 % decrease) in the SC tissue. Also, the capacity of oleic acid esterification was elevated in baseline state and with insulin stimulus in the PE tissue (+90 and 82 %, respectively). Likewise, spontaneous incorporation of lactate into lipids in the PE and SC tissues was higher (+100 and 11 %, respectively) in middle-aged rats. We concluded that adipocyte metabolism of middle-aged animals seems to strongly favor cellular hypertrophy and increased adipose mass, particularly the intra-abdominal PE fat pad. In discussion, we have interpreted all these results as a metabolic adaptations to avoid the spreading of fat that can reach tissues beyond adipose protecting them against ectopic fat accumulation. However, these adaptations may have the potential to lead to future metabolic dysfunctions seen in the senescence.     

Effects of dietary alpha- and gamma-linolenic acid on lipid metabolism in young and adult rats

The effect of age on lipid metabolism was studied in rats fed diets containing safflower oil (SFO, 78% linoleic acid), evening primrose oil (EPO, 9.4% gamma-linolenic acid and 70% linoleic acid) or the mixture of safflower and linseed oil (SLO, 10.2% alpha-linolenic acid and 68% linoleic acid). The activity of hepatic HMG-CoA reductase declined with age in all groups. In adult rats, the reductase activity was high in the EPO group and low in the SLO group. The activity of hepatic cholesterol 7 alpha-hydroxylase was independent of the diet or age. Hepatic delta 6-desaturase activity was low in adult rats fed EPO. In liver microsomal phospholipids, the percentage of 22:5 n-6 decreased while that of 22:6 n-3 increased with age. The ratio of linoleate metabolites to linoleate was high in the EPO group and low in the SLO group. Liver and serum cholesterol increased with age only in rats fed the SLO diet. Thus, the results indicated an enhanced susceptibility to dietary fats with age.     

肥胖者内脏脂肪蓄积与脂代谢的关系

目的:研究内脏脂肪蓄积与脂代谢的相关性。方法:选择首次就诊的163名单纯性肥胖病人。采用CT测定腹腔内脂肪面积,依据腹腔内脂肪面积分为内脏型肥胖组(腹腔内脂肪面积≥100cm2,115例)及皮下型肥胖组(腹腔内脂肪面积<100cm2,48例),并进行人体指标、脂代谢指标测定。结果:与皮下型肥胖组比较,内脏型肥胖组甘油三酯[TG,(1.69±1.51)mmol/L比(2.67±2.61)mmol/L]、总胆固醇[TC,(5.07±1.03)mmol/L比(5.65±1.19)mmol/L]水平显著升高(P<0.01),高密度脂蛋白胆固醇[HDL-C,(1.17±0.48)mmol/L比(1.02±0.22)mmol/L]水平显著降低(P<0.05)。直线相关分析显示,腹腔内脂肪面积与TG呈正相关(r=0.235,P=0.003),与HDL-C负相关(r=-0.162,P=0.039)。结论:内脏脂肪蓄积与脂代谢紊乱密切相关。     

Relation of body fat distribution to serum lipids and lipoproteins in elderly women

Fat distribution measured by dual photon absorptiometry, serum lipids and lipoproteins were determined in 95 elderly women with mild osteoporosis. Increasing obesity, determined anthropometrically as body mass index (BMI) = body weight/(height)2, was associated with a more central fat distribution (P less than 0.001) Central fat distribution correlated positively and independently of BMI and body weight to serum cholesterol, low density lipoprotein-cholesterol (LDL-C), triglycerides and the ratio LDL-C/HDL-C (P less than 0.05), whereas the correlation between central fat distribution and high density lipoprotein-cholesterol (HDL-C) was negative (P less than 0.05). We conclude that the increased risk of cardiovascular disease observed in subjects with central fat distribution might be partly mediated through changes in the lipoprotein profile.