Hepatocyte-Macrophage Acetoacetate Shuttle Protects against Tissue Fibrosis

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Genetic correlations between energy status indicator traits and female fertility in primiparous Nordic Red Dairy cattle

Inclusion of feed efficiency traits into the dairy cattle breeding programmes will require considering early lactation energy status to avoid deterioration in health and fertility of dairy cows. In this regard, energy status indicator (ESI) traits, for example, blood metabolites or milk fatty acids (FAs), are of interest. These indicators can be predicted from routine milk samples by mid-IR reflectance spectroscopy (MIR). In this study, we estimated genetic variation in ESI traits and their genetic correlation with female fertility in early lactation. The data consisted of 37 424 primiparous Nordic Red Dairy cows with milk test-day records between 8 and 91 days in milk (DIM). Routine test-day milk samples were analysed by MIR using previously developed calibration equations for blood plasma non-esterified FA (NEFA), milk FAs, milk beta-hydroxybutyrate (BHB) and milk acetone concentrations. Six ESI traits were considered and included: plasma NEFA concentration (mmol/l) either predicted by multiple linear regression including DIM, milk fat to protein ratio (FPR) and FAs C10:0, C14:0, C18:1 cis-9, C14:0 * C18:1 cis-9 (NEFA_FA) or directly from milk MIR spectra (NEFA_MIR), C18:1 cis-9 (g/100 ml milk), FPR, BHB (mmol/l milk) and acetone (mmol/l milk). The interval from calving to first insemination (ICF) was considered as the fertility trait. Data were analysed using linear mixed models. Heritability estimates varied during the first three lactation months from 0.13 to 0.19, 0.10 to 0.17, 0.09 to 0.14, 0.07 to 0.10, 0.13 to 0.17 and 0.13 to 0.18 for NEFA_MIR, NEFA_FA, C18:1 cis-9, FPR, milk BHB and acetone, respectively. Genetic correlations between all ESI traits and ICF were from 0.18 to 0.40 in the first lactation period (8 to 35 DIM), in general somewhat lower (0.03 to 0.43) in the second period (36 to 63 DIM) and decreased clearly (−0.02 to 0.19) in the third period (64 to 91 DIM). Our results indicate that genetic variation in energy status of cows in early lactation can be determined using MIR-predicted indicators. In addition, the markedly lower genetic correlation between ESI traits and fertility in the third lactation month indicated that energy status should be determined from the first test-day milk samples during the first 2 months of lactation.     

末梢血酮与尿酮在糖尿病酮症诊治中的临床应用价值比较

目的:比较末梢血酮即β-羟丁酸与尿酮在糖尿病酮症诊断和监测方面的临床价值。方法:收集2013年10月至2014年12月我院内分泌科收治的随机末梢血糖13.9 mmol/L的糖尿病患者161例,根据尿酮是否阳性分为糖尿病酮症患者29人,非糖尿病酮症患者132人。比较患者末梢血酮、尿酮的相关性;通过受试者工作特征曲线(ROC)寻找血酮诊断糖尿病酮症的诊断切点;比较血酮和尿酮对监测治疗反应性的优缺点。结果:糖尿病患者血酮和尿酮水平呈显著正相关,血酮随尿酮增加而增加(r=0.493,P0.001),而二者与血糖水平均无明显相关性(P=0.358,P=0.133)。以尿酮为糖尿病酮症诊断标准,ROC曲线下面积0.843(CI,0.746-0.939),末梢血酮诊断酮症的界值为0.25 mmol/L。在监测糖尿病酮症患者治疗的过程中,血酮较尿酮达峰更快,转阴更早。结论:血酮与尿酮有较好相关性,末梢血酮检测有良好的敏感性、及时性和精确性,对治疗策略有更好的指导意义,建议临床推广。     

The lipogenic enzyme acetoacetyl-CoA synthetase and ketone body utilization for denovo lipid synthesis,a review

Acetoacetyl-CoA synthetase (AACS) is the key enzyme in the anabolic utilization of ketone bodies (KBs) for denovo lipid synthesis, a process that bypasses citrate and ATP citrate lyase. This review shows that AACS is a highly regulated, cytosolic, and lipogenic enzyme and that many tissues can readily use KBs for denovo lipid synthesis. AACS has a low micromolar K_m for acetoacetate, and supply of acetoacetate should not limit its activity in the fed state. In many tissues, AACS appears to be regulated in conjunction with the need for cholesterol, but in adipose tissue, it seems tied to fatty acid synthesis. KBs are readily utilized as substrates for lipid synthesis in lipogenic tissues, including liver, adipose tissue, lactating mammary gland, skin, intestinal mucosa, adrenals, and developing brain. In numerous studied cases, KBs served several-fold better than glucose as substrates for lipid synthesis, and when present, KBs suppressed the utilization of glucose for lipid synthesis. Here, it is hypothesized that a physiological role for the utilization of KBs for lipid synthesis is a metabolic process of lipid interconversion. Fatty acids are converted to KBs in liver, and then, the KBs are utilized to synthesize cholesterol and other long-chain fatty acids in liver and nonhepatic tissues. The conversion of fatty acids to cholesterol via the KBs may be a particularly important example of lipid interconversion. Utilizing KBs for lipid synthesis is glucose sparing and probably is important with low carbohydrate diets. Metabolic situations and tissues where this pathway may be important are discussed.