Differential Roles of Breakfast and Supper in Rats of a Daily Three-Meal Schedule Upon Circadian Regulation and Physiology

The timing of meals has been suggested to play an important role in circadian regulation and metabolic health. Three meals a day is a well-established human feeding habit, which in today's lifestyle may or may not be followed. The aim of this study was to test whether the absence of breakfast or supper significantly affects the circadian system and physiological function. The authors developed a rat model for their daily three meals study, whereby animals were divided into three groups (three meals, TM; no first meal, NF; no last meal, NL) all fed with the same amount of food every day. Rats in the NF group displayed significantly decreased levels of plasma triglyceride (TG), total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), and glucose in the activity phase, accompanied by delayed circadian phases of hepatic peripheral clock and downstream metabolic genes. Rats in the NL group showed lower concentration of plasma TC, HDL-C, and glucose in the rest phase, plus reduced adipose tissue accumulation and body weight gain. Real-time polymerase chain reaction (PCR) analysis indicated an attenuated rhythm in the food-entraining pathway, including down-regulated expression of the clock genes Per2, Bmal1, and Rev-erbα, which may further contribute to the delayed and decreased expression of FAS in lipogenesis in this group. Our findings are consistent with the conclusion that the daily first meal determines the circadian phasing of peripheral clocks, such as in the liver, whereas the daily last meal tightly couples to lipid metabolism and adipose tissue accumulation, which suggests differential physiological effects and function of the respective meal timings. (Author correspondence: azwfu2003@yahoo.com.cn)     

Circadian Mechanisms of Food Anticipatory Rhythms in Rats Fed Once or Twice Daily: Clock Gene and Endocrine Correlates

Circadian clocks in many brain regions and peripheral tissues are entrained by the daily rhythm of food intake. Clocks in one or more of these locations generate a daily rhythm of locomotor activity that anticipates a regular mealtime. Rats and mice can also anticipate two daily meals. Whether this involves 1 or 2 circadian clocks is unknown. To gain insight into how the circadian system adjusts to 2 daily mealtimes, male rats in a 12∶12 light-dark cycle were fed a 2 h meal either 4 h after lights-on or 4 h after lights-off, or a 1 h meal at both times. After 30 days, brain, blood, adrenal and stomach tissue were collected at 6 time points. Multiple clock genes from adrenals and stomachs were assayed by RT-PCR. Blood was assayed for corticosterone and ghrelin. Bmal1 expression was quantified in 14 brain regions by in situ hybridization. Clock gene rhythms in adrenal and stomach from day-fed rats oscillated in antiphase with the rhythms in night-fed rats, and at an intermediate phase in rats fed twice daily. Corticosterone and ghrelin in 1-meal rats peaked at or prior to the expected mealtime. In 2-meal rats, corticosterone peaked only prior the nighttime meal, while ghrelin peaked prior to the daytime meal and then remained elevated. The olfactory bulb, nucleus accumbens, dorsal striatum, cerebellum and arcuate nucleus exhibited significant daily rhythms of Bmal1 in the night-fed groups that were approximately in antiphase in the day-fed groups, and at intermediate levels (arrhythmic) in rats anticipating 2 daily meals. The dissociations between anticipatory activity and the peripheral clocks and hormones in rats anticipating 2 daily meals argue against a role for these signals in the timing of behavioral rhythms. The absence of rhythmicity at the tissue level in brain regions from rats anticipating 2 daily meals support behavioral evidence that circadian clock cells in these tissues may reorganize into two populations coupled to different meals.     

Circadian clocks for all meal-times: anticipation of 2 daily meals in rats

Anticipation of a daily meal in rats has been conceptualized as a rest-activity rhythm driven by a food-entrained circadian oscillator separate from the pacemaker generating light-dark (LD) entrained rhythms. Rats can also anticipate two daily mealtimes, but whether this involves independently entrained oscillators, one 'continuously consulted' clock, cue-dependent non-circadian interval timing or a combination of processes, is unclear. Rats received two daily meals, beginning 3-h (meal 1) and 13-h (meal 2) after lights-on (LD 14:10). Anticipatory wheel running began 68±8 min prior to meal 1 and 101±9 min prior to meal 2 but neither the duration nor the variability of anticipation bout lengths exhibited the scalar property, a hallmark of interval timing. Meal omission tests in LD and constant dark (DD) did not alter the timing of either bout of anticipation, and anticipation of meal 2 was not altered by a 3-h advance of meal 1. Food anticipatory running in this 2-meal protocol thus does not exhibit properties of interval timing despite the availability of external time cues in LD. Across all days, the two bouts of anticipation were uncorrelated, a result more consistent with two independently entrained oscillators than a single consulted clock. Similar results were obtained for meals scheduled 3-h and 10-h after lights-on, and for a food-bin measure of anticipation. Most rats that showed weak or no anticipation to one or both meals exhibited elevated activity at mealtime during 1 or 2 day food deprivation tests in DD, suggesting covert operation of circadian timing in the absence of anticipatory behavior. A control experiment confirmed that daytime feeding did not shift LD-entrained rhythms, ruling out displaced nocturnal activity as an explanation for daytime activity. The results favor a multiple oscillator basis for 2-meal anticipatory rhythms and provide no evidence for involvement of cue-dependent interval timing.     

血压、血脂、血糖、同型半胱氨酸及超敏C反应蛋白水平与脑梗死发病危险性的关系

目的:探讨血压、血脂、血糖、糖化血红蛋白、同型半胱氨酸(HCY)和超敏C反应蛋白(hs-CRP)与脑梗死发病危险性的相关性,为及时防止脑梗死的发病及早期诊断脑梗死提供理论依据。方法:采用回顾性病例对照研究,用全自动生化分析仪器检测各项生化指标,并运用SPSS 20.0软件包对256例脑梗死患者和216例健康对照者的血生化指标进行统计分析。同时,将脑梗死组分为三组:单纯脑梗死组、合并高血压组、合并糖尿病组,分别与正常对照组进行血脂水平的分析比较。结果:血压、总胆固醇(TC)、三酰甘油(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇酯(HDL-C)、同型半胱氨酸(HCY)、血糖、hs-CRP水平和总胆固醇/高密度脂蛋白胆固醇(TC/HDL-C)比值在病例组和对照组间有显著性差异(P0.05)。同时,在三组不同的病例组中血脂(TC、TG、LDL-C、TC/HDL-C)水平和HCY水平明显高于正常对照组,而HDL-C水平则明显低于对照组。(P0.05)。结论:高血压、高血糖、HCY、hs-CRP水平增高及血脂异常均与脑梗死发病危险性相关,联合检测上述指标对预防及治疗脑梗死均有重要意义。     

9758 例健康体检者血糖与血脂的关系分析

目的:探讨健康体检人群血糖与血脂现况及两者之间的相关性。方法:采集我院9758例健康体检者的空腹静脉血,检测其空腹血糖(FPG)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白(HDL-C)和低密度脂蛋白(LDL-C)水平,比较不同FPG水平组间各血脂水平,分析FPG水平与血脂的相关性。结果:各年龄组FPG、TC、TG、HDL-C和LDL-C水平差异均具有统计学意义(P0.05);FPG均与TC、TG和LDL-C水平呈现正相关(r=0.127,0.189,0.141,P0.005),而与HDL-C呈现负相关(r=-0.112,P0.005);根据FPG水平由高到低分为糖尿病(DM)组,血糖调节受损(IFG)组及血糖正常组,其中对TC和LDL-C水平异常率而言,IFG组DM组血糖正常组;对TG、HDL-C水平异常率而言,DM组IFG组血糖正常组。结论:健康人群中血糖和血脂水平呈现一定的相关性,两者的水平异常会增加慢性疾病的发生风险。     

进口普罗布考治疗高脂血症的疗效观察

目的:观察进口普罗布考对高脂血症患者的降脂作用,并评价其疗效。方法:纳入符合要求的高脂血症患者264例,应用优效性设计,并随机分为实验组(普罗布考)和对照组(安慰剂),其中实验组127例,对照组137例。检测总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、氧化低密度脂蛋白(oxLDL)等血脂指标;分别于访视0、访视2、访视3时进行测量,共观察8周。结果:实验后4周及8周TC与LDL-C均较实验前降低,且普罗布考对TC和LDL-C的降低作用明显优于安慰剂;实验后4周及8周oxLDL在两组间均无明显降低,且试验后普罗布考与安慰剂组间无差异;实验后4周及8周普罗布考对TG均有降低趋势,但是与安慰剂相比没有统计学意义;而普罗布考降低HDL-C较安慰剂显著。结论:本试验证实进口普罗布考对降低中国高血脂症患者血脂中TC、LDL-C、HDL-C有明显作用,适宜推广。     

The antilipemic effectiveness of pentaerythritol tetranicotinate on hyperlipidemic patients with or without diabetes mellitus--a double-blind, randomized and two-period change-over experiment

Pentaerythritol tetranicotinate (Perycit), at an oral dosage of 750 mg daily, was given to 12 patients with idiopathic hyperlipidemia and to 12 patients with hyperlipidemia superimposed with diabetes mellitus (DM). With 2 months off-drug period as the baseline, each patient then received 3 months of placebo and 3 months of Perycit. The sequence of treatment was randomized and balanced in frequency. Blood glycosylated hemoglobin (Hb A1) and fasting plasma glucose (FPG) were used as indices of diabetic control. Serum triglyceride (TG), total cholesterol (TC), high density lipoprotein cholesterol (HDL-C), and TC/HDL-C ratio were measured and calculated in order to compare the antilipemic effectiveness of Perycit with that of placebo. The non-parametric Wilcoxon test was used for the statistical analysis. The results showed that in the idiopathic group, Perycit significantly lowered the serum level of TG and the ratio of TC/HDL-C, and elevated the serum level of HDL-C. In the diabetic group, although there was a similar improvement in diabetic control in both periods of placebo and Perycit treatments, there was no change in the serum levels of TG and HDL-C. There was a slight increase of the serum levels of TC in the periods of Perycit treatment, whereas a small increase of HDL-C resulted in a mild decrease of the TC/HDL-C ratio. There was mild and transient facial flushing during the Perycit treatment in 6 out of 12 diabetic patients. Otherwise, there was no side effects in either group. Pooling the two groups' data together, Perycit increased the serum levels of HDL-C and decreased the TC/HDL-C ratio. It is concluded that Perycit has antilipemic effects in patients with idiopathic hyperlipidemia, and may be helpful in reducing the atherogenic risks in these patients. In patients with hyperlipidemia superimposed with DM, although the serum lipids composition was not significantly changed after Perycit, the atherogenic risks might also be reduced as demonstrated by the decrease of the TC/HDL-C ratio.     

内脏脂肪组织沉默信息调节因子1在高脂诱导西藏小型猪胰岛素抵抗中的表达研究*

目的: 探讨内脏脂肪组织沉默信息调节因子1(Sirt1)在高脂诱导西藏小型猪肥胖和胰岛素抵抗中的表达。方法: 12只雄性西藏小型猪,随机分为正常对照组(NC)和高脂组(HFC),每组6只。造模16周后,测量空腹体重、体质量指数(BMI),并取前腔静脉血,测量总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)和高密度脂蛋白胆固醇(HDL-C),计算动脉硬化指数(AI);同时,进行静脉糖耐量实验。在动物进行安乐死后,检测内脏脂肪率,并取内脏脂肪组织进行病理组织学观察和脂肪细胞直径大小分析,并采用RT-PCR法观察脂肪组织中Sirt1、胰岛素样生长因子-1(IGF-1)、葡萄糖转运蛋白4(GLUT4)、过氧化物酶体增殖物激活受体γ(PPARγ)、过氧化物酶体增殖活化受体γ辅助活化因子1α(PGC-1α)、叉头框蛋白O1(FoxO1)、脂肪分解相关基因激素敏感性脂肪酶(HSL)及脂肪合成相关基因脂肪酸合成酶(FASN)的mRNA水平变化。结果: 与NC组比较,HFC组体重、BMI指数、TC、LDL-C、HDL-C、AI和内脏脂肪率均显著升高(P＜0.05,P＜0.01);同时,糖耐量曲线明显延迟并且血糖和胰岛素曲线下面积均显著升高(P＜0.05);HE病理观察和定量分析显示,脂肪细胞肥大且平均细胞直径明显增加(P＜0.01);另外,脂肪组织中Sirt1、PGC-1α 、GLUT4、HSL mRNA水平均有不同程度的降低,其中Sirt1和HSL mRNA表达显著降低(P ＜0.05),FOXO1、IGF-1、PPAR-γ和FASN mRNA表达则显著升高(P＜0.05, P＜0.01)。结论: 高脂饮食诱导西藏小型猪能形成肥胖模型,并具有脂质紊乱和胰岛素抵抗等表型特征;而Sirt1在内脏脂肪沉积和胰岛素敏感性降低中起着关键作用。     

Effect of cod liver oil supplementation on plasma lipids, lipoproteins, lipase activity and platelet aggregation in normotensive and hypertensive volunteers

No significant change in plasma levels of total cholesterol (TC), triglycerides, phospholipids, very-low-density lipoprotein cholesterol, low-density lipoprotein cholesterol, high-density lipoprotein cholesterol (HDL-C), lipase activity and TC/HDL-C ratio could be observed in both normotensive and hypertensive individuals after cod liver oil supplementation. Measure of platelet aggregation rates did not also show any significant change after cod liver oil ingestion in both normotensive and hypertensive individuals. The results suggest that supplementation of normal diets with 600 mg cod liver oil per day for 50 days neither affects plasma lipids, lipoproteins and lipase activity nor affects platelet aggregation in both normotensive and hypertensive individuals.     

成人原发肾病综合征病理类型与血脂代谢紊乱的关系

目的：研究成人原发肾病综合征(PNS)肾脏病理改变与血脂代谢紊乱的关系。方法：选取成人PNS患者109 例为研究对象, 分析不同病理类型PNS 患者血脂及血清脂蛋白代谢异常的发生率、代谢水平及胆固醇代谢异常的相关因素。结果：成人PNS 患 者血清总胆固醇(TC)升高、低密度脂蛋白胆固醇(LDL-C)升高、高密度脂蛋白胆固醇(HDL-C)降低、甘油三酯(TG)升高的发生率分 别为89.90%、69.72%、9.17%、41.28%,高胆固醇血症占51.37%,混合型高脂血症占39.45%;微小病变型肾病(MCD)、膜性肾病 (MN)、系膜增生性肾小球肾炎(MsPGN)、局灶阶段性肾小球硬化(FSGS)组间TC、TG、LDL-C、HDL-C 代谢异常发生率及代谢水平 比较均无明显差别(P>0.05);病理类型为MCD 及n-MCD 的PNS 患者,胆固醇水平均与24 小时尿蛋白定量呈正相关(r=0.440, P=0.036;r=0.361,P=0.001),与血白蛋白水平无明显相关性(P>0.05)。结论：成人PNS患者血脂代谢异常以TC 及LDL-C 升高为 主,临床分型中以高胆固醇血症及混合型高脂血症为主;病理类型为MCD及n-MCD 的PNS 患者,胆固醇水平均与24 小时尿蛋 白呈正相关,与血白蛋白水平无明显相关性。     

皖南花猪11种血液生化指标的发育性变化及性别差异

随机选择出生30、45、90、180日龄的皖南花猪公母各5头,测定了11项血清生化指标.结果显示:血糖(GLU)、总胆固醇(TC)、高密度脂蛋白胆固醇(HDL-C)、游离脂肪酸(FFA)、脂联素(ADP)、瘦素(leptin)和IgG有极显著的发育性变化(P0.01);而甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)、IgA和IgM等没有明显的发育性变化.母猪的TG、TC、HDL-C和IgM极显著或显著大于公猪(P0.01或P0.05),其他血清生化指标虽在总体上没有性别差异,但在有些日龄差异明显,大多表现为母猪在90或180日龄大于公猪.结果表明:皖南花猪血液生化指标有特定的发育性模式,并存在不同程度的性别差异.     

冠心病患者的血脂、胆红素、UA及Fib水平变化及临床意义

目的:研究冠心病(CHD)患者的血脂、胆红素、血尿酸(UA)及纤维蛋白原(Fib)水平变化及临床意义。方法:选取2014年4月到2015年4月我院收治的CHD患者110例(研究组),另选取同期健康体检者110例(对照组),检测两组受检者血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C)、直接胆红素(DBIL)、间接胆红素(IBIL)、总胆固醇(TBIL)、UA以及Fib水平。结果:研究组TC、TG、LDL-C、UA以及Fib水平均显著高于对照组,两组比较差异具有统计学意义(P0.05);研究组HDL-C、DBIL、IBIL以及TBIL均显著低于对照组,两组比较差异具有统计学意义(P0.05)。结论:血脂水平异常,胆红素水平降低,UA以及Fib水平增高与CHD的发病有关。     

High‐fat Diet Followed by Fasting Disrupts Circadian Expression of Adiponectin Signaling Pathway in Muscle and Adipose Tissue

The circadian clock controls energy homeostasis by regulating circadian expression of proteins involved in metabolism. Disruption of circadian rhythms leads to obesity and metabolic disorders. Little is known regarding the control of the biological clock over adiponectin signaling pathway in adipose tissue, the adiponectin producer, and muscle, an adiponectin target tissue under fasting, low‐fat (LF), or high‐fat (HF) diet. Mice were fed LF or HF diet for 7 weeks and fasted on the last day. The circadian mRNA expression of clock genes and components of adiponectin metabolic pathway (mAdipoR1, mAdipoR2, mPparα, mPparγ, mAmpk, and mAcc) in the muscle and adipose tissue were tested. Using average daily levels of multiple time points around the circadian cycle, we assessed mRNA levels of the different adiponectin signaling components. In addition, serum glucose, adiponectin, and insulin were measured. Under LF diet, adiponectin signaling pathway components exhibited circadian rhythmicity at the mRNA levels. Fasting and HF diet followed by fasting disrupted this circadian expression causing a phase advance or delay, respectively. Changes were also found in the expression levels of adiponectin receptor, mAmpk, mAcc, mPparα, and mPparγ reflecting a defect in adiponectin signaling. As both peroxisome proliferator‐activated receptor α (PPARα) and mAMPK are linked to the core clock mechanism, they could mediate the disruptions seen in clock gene expression under HF diet. In turn, the circadian clock affects the daily rhythm of these adiponectin signaling components.     

川芎嗪注射液对冠心病心绞痛患者血脂相关指标的影响及其临床疗效分析

目的:探讨川芎嗪注射液治疗冠心病心绞痛的临床疗效。方法:选择2014年5月-2016年5月在我院接受治疗的冠心病心绞痛患者79例,根据治疗方法不同分为对照组(37例)和研究组(42例)。对照组患者给予常规治疗,研究组患者在对照组基础上给予川芎嗪注射液治疗。观察并比较两组患者的临床疗效。结果:治疗前,两组患者总胆固醇(TC)、甘油三酯(TG)、低密度脂蛋白胆固醇(LDL-C)及高密度脂蛋白胆固醇(HDL-C)水平比较,差异无统计学意义(P0.05);治疗后,两组患者总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白胆固醇(LDL-C)水平均显著降低,差异具有统计学意义(P0.05);治疗后,研究组患者总胆固醇(TC)、甘油三酯(TG)及低密度脂蛋白胆固醇(LDL-C)水平均低于对照组,差异具有统计学意义(P0.05);治疗后,两组患者高密度脂蛋白胆固醇(HDL-C)水平比较,差异无统计学意义(P0.05)。研究组患者治疗总有效率(92.86%)高于对照组(81.08%),差异具有统计学意义(P0.05)。结论:川芎嗪注射液治疗冠心病心绞痛的临床疗效显著,能够降低血脂相关指标水平,改善临床症状,值得临床推广应用。     

Correlation among clock gene expression rhythms,sleep quality,and meal conditions in delayed sleep-wake phase disorder and night eating syndrome

Clock genes that comprise the circadian clock system control various physiological functions. Delayed sleep-wake phase disorder (DSWPD) and night eating syndrome (NES) are characterized by delayed sleep and meal timing, respectively. We estimated that clock gene expression rhythms in DSWPD patients may be delayed in comparison with the healthy subjects due to delayed melatonin secretion rhythms, producing eveningness chronotype in these individuals. However, it was difficult to estimate which clock gene expression rhythms were delayed or not in NES patients, because previous studies revealed that melatonin secretion rhythm was a little delayed compared with healthy individuals and that chronotype of NES patients depended on the individuals. Therefore, we examined expression rhythms of clock genes such as Period3 (Per3), nuclear receptor subfamily 1, group D, member 1 (Nr1d1) and Nr1d2 in these patients. Further, we expected sleep and meal patterns in DSWPD and NES patients may be more diverse than patterns observed in healthy subjects, and thus analyzed relationships among clock gene expression rhythms, sleep quality, sleep midpoint time, and meal times. We enrolled healthy male participants along with DSWPD and NES male patients, and asked all participants to answer questionnaires and to keep diaries to record information on their sleep and meals. Further, we asked them to collect 5–10 beard follicle samples, 6 times every 4 h. We measured clock gene expression rhythms using total RNA extracted from beard follicle cells. Peak time of clock gene expression in the NES group showed more diversity than the other groups, and that in the DSWPD group was delayed compared with the control group. In addition, the peak time of clock gene expression was negatively correlated with sleep quality and positively correlated with meal time after a long fast. Amplitudes of clock gene expression, especially Per3, positively responded to better mental and physical conditions as well as with better sleep quality. Results of this study suggest that peak times of clock gene expression in NES patients depended on the individuals; some patients with NES showed similar clock gene expression rhythm to healthy subjects, and other patients with NES showed similar to DSWPD patients. Moreover, this study suggests that meal time after a long fast may influence more determination in clock gene expression rhythms than the time of breakfast. Therefore, this study also indicates that Per3 clock gene may be one of the parameters that will help us understand sleep and meal rhythm disturbances.     

不同性别间颈动脉粥样硬化相关危险因素差异的研究

目的:探讨中年人群中不同性别间颈动脉粥样硬化相关危险因素的差异。方法:将104例中年颈动脉粥样硬化患者作为研究对象,其中男53例,女51例,比较两组体质量指数(BMI)、收缩压(SBP)、舒张压(DBP)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、脂蛋白(a)[Lp(a)]、空腹血糖(FBG)、血尿酸(UA)、超敏CRP(hs-CRP)的差异。结果:男性组BMI、TG、UA较女性组高,HDL-C、Lp(a)较女性组低,差异有统计学意义(P<0.05)。结论:有些颈动脉粥样硬化相关危险因素在不同性别中年人群中具有差异。     

Effect of diazinon, an organophosphate insecticide, on plasma lipid constituents in experimental animals

There has been increasing interest in studying the various effects of organophosphate insecticides in humans and experimental animals. Only a few data are available on the effect of the organophosphate insecticide, diazinon, on lipid metabolism. The aim of this study was to evaluate the effect of diazinon on plasma lipid constituents in mammalian animals. The plasma levels of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), and phospholipids (PL) were measured in albino rats that were orally treated with a single dose of diazinon at a level of LD(50) or with repeated daily doses at the levels of 1/2, 1/8, and 1/32 LD(50) for 2, 8, and 32 days, respectively. After a 24 h post-treatment with a single LD(50) dose of diazinon, TC was not significantly changed, the HDL-C and PL levels were significantly decreased, but the LDL-C and TG levels were significantly increased. Separate daily oral administrations of diazinon at 1/2 LD(50), 1/8 LD(50), and 1/32 LD(50) doses resulted in a significant decrease in HDL-C and PL, with no significant change in TG. The LDL-C levels were significantly increased and TC showed no significant change with 1/2 LD(50) and 1/32 LD(50) doses of diazinon, whereas a significant decrease in the levels of TC, HDL-C, as well as LDL-C, was observed with the 1/8 LD(50) dose. These data suggest that diazinon may interfere with lipid metabolism in mammals.