A Comparison of Bone Mineral Density and Its Predictors in HIV-Infected and HIV-Uninfected Older Men

ObjectiveBone health in older individuals with HIV infection has not been well studied. This study aimed to compare bone mineral density (BMD), trabecular bone score (TBS), and bone markers between HIV-infected men and age- and body mass index (BMI)-matched HIV-uninfected men aged ≥60 years. We investigated the associations of risk factors related to fracture with BMD, TBS, and bone markers in HIV-infected men.MethodsThis cross-sectional study included 45 HIV-infected men receiving antiretroviral therapy and 42 HIV-uninfected men. Medical history, BMD and TBS measurements, and laboratory tests related to bone health were assessed in all the participants. HIV-related factors known to be associated with bone loss were assessed in the HIV-infected men.ResultsThe mean BMD, TBS, and osteopenia or osteoporosis prevalence were similar among the cases and controls. The HIV-infected men had significantly higher mean N-terminal propeptide of type 1 procollagen and C-terminal cross-linking telopeptide of type I collagen levels. Stepwise multiple linear regression analysis demonstrated that low BMI (lumbar spine, P = .015; femoral neck, P = .018; and total hip, P = .005), high C-terminal cross-linking telopeptide of type I collagen concentration (total hip, P = .042; and TBS, P = .010), and low vitamin D supplementation (TBS, P = .035) were independently associated with low BMD and TBS.ConclusionIn older HIV-infected men with a low fracture risk, the mean BMD and TBS were similar to those of the age- and BMI-matched controls. The mean bone marker levels were higher in the HIV group. Traditional risk factors for fracture, including low BMI, high C-terminal cross-linking telopeptide of type I collagen level, and low vitamin D supplementation, were significant predictors of low BMD and TBS.     

Decreased brown adipose tissue thermogenic activity following a reduction in brain serotonin by intraventricular p-chlorophenylalanine

The effects of reducing brain serotonin (5-HT) levels by means of intracerebral-ventricular injections of the tryptophan antagonist p-chlorophenylalanine (PCPA) were investigated in male rats. Six days after the operation, PCPA-treated rats, either fedad libitum or pair-fed to the food intake of control rats, showed decreased thermogenic activity and capacity in their interscapular brown adipose tissue (BAT) and also increased fat storage in their white adipose tissue (WAT). These results indicate that serotonergic synapses might play a regulatory role in the sympathetic control of BAT thermogenesis and in the rate of WAT deposition (by an as yet unidentified mechanism), in addition to their well established role in controlling food intake.     

躯体和内脏传入冲动在大鼠束旁核内的会聚

在麻痹的大鼠上,分别刺激迷走神经、内脏大神经、坐骨神经、腓肠神经、睾丸和副睾,在对侧丘脑束旁核记录到了45个细胞的单位放电。根据诱发反应的潜伏期、时程和放电频谱分布的不同,可将他们分为五种类型,并且认为这些类型和刺激引起的感觉性质有关。在观察到的45单位中,29个的反应具有痛放电的特性,而且对躯体及内脏的传入冲动呈聚合性反应。其中2个单位只对内脏传入冲动产生反应。这项研究的结果表明,束旁核不仅是接受内脏传入的丘脑结构,而且也是一个整合内脏与躯体传入信息的中枢。     

Effect of noradrenaline chronic administration on brown fat phospholipids

Chronic cold exposure of rats (9 days at 5°C) induces an alteration of the fatty acid composition of phospholipids in brown adipose tissue. The alteration is due to an increase of the unsaturation degree of these lipids. The phenomenon can be reproduced by 10^–7 mole. h^–1 administration of noradrenaline for 9 days in rats kept at 25°C. Thus, phospholipid alteration in brown fat of cold exposed rats is most probably a consequence of the increase of sympathetic tone which occurs in this tissue during exposure to cold.     

对冷适应大鼠棕色脂肪和肝脏在非寒颤产热机制中作用的评价

本实验主要观察并比较了大鼠冷适应前后直肠温度(RT)、血清游离脂肪酸(SFFA)浓度、肩胛间棕色脂肪组织(IBAT)和肝脏cAMP含量的变化及其对去甲肾上腺素(NE)反应性的改变。结果表明:①冷适应28d大鼠在冷环境中RT稳定,NE刺激后RT上升幅度大于常温对照组(P<0.005);②冷适应1d组SFFA升高,冷适应28d组SFFA接近对照组,且对NE刺激无反应,对照组给NE后SFFA与RT一致性升高;③冷适应28d组IBAT的cAMP升高,而肝脏的cAMP含量三组间无显著性差异。NE刺激后,冷适应28d组IBAT和肝脏cAMP均升高,与RT反应一致,而对照组不变。结果提示,在5±3℃适应28d的大鼠已建立冷适应机制,非寒颤产热(NST)容量增加,在冷适应的不同时期,肝脏和IBAT调节NST的机制不同。     

The role of NADPH in the regulation of glucose-6-phosphate and 6-phosphogluconate dehydrogenases in rat adipose tissue

Summary Previous studies examining the regulation of the synthesis of G6PDH and 6PGDH in rat liver and adipose tissue have focused on the induction of these enzymes by different diets and some hormones. In rat liver these enzymatic activities seem to be regulated by a mechanism involving changes in the NADPH requirements. In this paper we have studied the effect of changes in the flux through different NADPH-consuming pathways on G6PDH and 6PGDH levels in adipose tissue and on the NADPH/NADP ratio. The results show that: I) an increase in the consumption of NADPH, caused by the activation of either fatty acid synthesis or detoxification systems which consume NADPH, is paralleled by an increase in the levels of these enzymes; II) when the increase in consumption of NADPH is prevented, the G6PDH and 6PGDH levels do not change.Abbreviations G6PDH Glucose-6-Phosphate Dehydrogenase - 6PGDH 6-Phosphogluconate Dehydrogenase - GR Glutathione Reductase - ME Malic Enzyme - tBHP t-Butyl Hydroperoxide - NF Nitrofurantoin - CumOOH Cumene Hydroperoxide     

Evidence that fasting can induce a selective loss of uncoupling protein from brown adipose tissue mitochondria of mice

The effects of fasting and refeeding on the concentration of uncoupling protein in brown adipose tissue mitochondria have been investigated in mice. Fasting mice for 48 h led to a large decrease in the total cytochrome oxidase activity of the interscapular brown fat pad. Mitochondrial GDP binding and the specific mitochondrial concentration of uncoupling protein also fell on fasting. After 24 h refeeding both GDP binding and the mitochondrial concentration of uncoupling protein were normalized, but there was no alteration in the total tissue cytochrome oxidase activity. Fasting appears to induce a selective loss of uncoupling protein from brown adipose tissue mitochondria, which is rapidly reversible on refeeding.     

Growth of epithelium from a preneoplastic mammary outgrowth in response to mammary adipose tissue

Summary We investigated the effects of conditioned media derived from mouse mammary fat pads on the proliferation of CL-S1 cells, an epithelial cell line originally isolated from a preneoplastic mammary outgrowth line. Cell proliferation in vitro in serum-free defined medium was compared to that in this medium conditioned using intact mammary fat pad pieces or isolated fat pad adipocytes. Culture medium was conditioned by incubating the conditioning material in defined culture medium for 24 h at 37°C. Conditioned medium induced CL-S1 proliferation as much as 10- to 20-fold above the minimal levels of growth in control cultures after 13 d of culture. The growth-stimulatory factor(s) had an apparent molecular weight of greater than 10 kDa. This growth-stimulatory activity was both heat and trypsin stable. Because the role of adipose tissue is to store and release lipids, we next tested whether lipids are released during medium conditioning. The lipid composition of the fat pad conditioned medium was characterized using both thin layer and gas liquid chromatography. These lipid analyses indicated that the fat pad pieces released significant amounts of fatty acids and phospholipids into the medium during the conditioning period. The free fatty acid composition included both saturated and unsaturated molecules, and about 80% of the total fatty acids consisted of palmitate, stearate, oleate, and linoleate. These same fatty acids were a structural component of the majority of phospholipid found in the medium. The addition of palmitate or stearate to defined medium had no effect or was inhibitory for CL-S1 proliferation, depending on the concentration used. Defined medium supplemented with oleate, arachidonate, or linoleate induced CL-S1 proliferation, and the inhibitory effects of palmitate and stearate were overcome by addition of oleate and linoleate. These data indicate that both unsaturated and saturated fatty acids are released from intact adipose cells of the mouse mammary fat pad and that fatty acids can influence the growth of prenoplastic mouse mammary epithelium. Thus, unsaturated fatty acids, perhaps in conjunction with other substances released simultaneously, are candidate molecules for the substances that mediate the effect of adipose tissue on growth of epithelium. This work was supported in part by a grant from the American Institute for Cancer Research; grant CA 46885 from the National Institutes of Health, Bethesda, MD; and by State of Washington initiative 171.     

The stroma-vascular fraction of rat inguinal and epididymal adipose tissue and the adipoconversion of fat cell precursors in primary culture

The stroma-vascular fraction (SVF) of inguinal and epididymal fat pads of 4 week-old rats was studied by electron microscopy. Among the various cell types, endothelial cells and preadipocytes were found in both SVF, while mesothelial cells were only detected in the epididymal SVF. The resulting heterogeneity of primary culture and the adipoconversion of the fat cell precursors were studied in a serum-supplemented medium enriched with insulin (14.5 nM) and exogenous triglycerides. Despite the heterogeneity of the inoculum, the primary cultures were rather homogeneous, fat cell precursors being the main cell type. Distinctive contaminant fibroblast-like cells were observed in both cultures, whereas epithelial-like cells, which correspond most probably to mesothelial cells, were only found in epididymal cultures. Differentiation of fat cell precursors was assessed by the appearance of lipoprotein lipase (LPL) and glycerol-3-phosphate dehydrogenase (GPDH). LPL activity was found in the same level in cells of both deposits while GPDH activity was elevated in inguinal vs epididymal derived stroma-vascular cells. The different adipose conversion pattern of both cultures was confirmed by morphological quantification: the maturation of epididymal fat cell precursors was faster but less extensive. These differences could be related mainly to regional localization rather than to different maturation of the two fat deposits.     

The role of β- and α-adrenoreceptors on blood flow and temperature of brown adipose tissue and involvement of nitric oxide in their effects

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2. 1. Isoproterenol increased interscapular brown adipose tissue (BAT) blood flow and temperature.

3. 2. Phenylephrine increased BAT temperature, but did not affect blood flow. The effect was completely suppressed by N^ω-nitro- -arginine methyl ester ( -NAME), an inhibitor of endogenous NO synthesis.

4. 3. Isoproterenol plus phenylephrine increased BAT blood flow and temperature earlier than isoproterenol alone.

5. 4. CL316,243 increased BAT blood flow and temperature. These effects were also inhibited by -NAME.

6. 5. These data suggest that BAT blood flow as well as thermogenesis is regulated mainly by β-adrenoreceptors and partly by α₁-adrenoreceptors, and NO may be a common mediator for their regulations.