Novel N-Acylethanolamide Derivatives Affect Body Weight and Energy Balance

Introduction – The obesity pandemic is multifactorial. Nutritional, pharmacologic and surgical interventions are limited in reach and efficacy, raising need for new therapeutics. Aims – Characterization of anorexigenic and cognitive effect and central mechanism of action of novel N-acylethanolamide derivatives. Methods – Sabra mice divided to similar experimental groups, injected IP with: oleyl-L-leucinolamide ( 1 A ), linoleyl-L-leucinolamide ( 4 A ), linoleyl-L-valinolamide ( 5 A ), oleyl-oxycarbonyl-L-valinolamide ( 1 B ), oleyl-oxycarbonyl-D-valinolamide ( 2 B ), oleylamine-carbonyl-L-valinolamide ( 3 B ), oleylamine-carbonyl-D-valinolamide ( 4 B ), and oleyl-L-hydroxyvalineamide ( 5 B ). Control group with vehicle. Body weight and food consumption followed for 39 days. Motor activity and cognitive function by open field test and eight-arm maze. Mice sacrificed and mechanism of action investigated by qPCR. The genes analyzed involved in energy balance and regulation of appetite. Catecholamines and serotonin evaluated. Results – Compounds 1 A , 5 A , 1 B – 4 B , caused significant weight loss of 4.2–5.6 % and 5 A , 1 B – 4 B , improved cognitive function following 8 i. p. injections of 1 mg/kg during 39 days, by different mechanisms. 5 A , 3 B and 4 B decreased food consumption, whereas 1 A , 5 A and 2 B increased motor activity. 1 A , 4 A , 1 B and 3 B elevated SIRT-1, associated with survival. POMC upregulated by 1 B and 2 B , CART by 1 B , 2 B and 1 A . NPY and CAMKK2 downregulated by 5 A . 4 B enhanced 5-HT levels. 4 A , 5 A , 1 B , 4 B , 5 B decreased FAAH, showing long lasting effect. Conclusions – These new compounds might be developed for the treatment of obesity and for improved cognitive function.     

多次短时间快走能提高机体脂肪和能量的消耗

为探讨多次短时间及单次长时间的快走对脂肪代谢与激素反应的影响,以提高鼓励运动的说服力,本研究选择15名健康大学男生为研究对象,进行单次长时间快走运动(SL)(1次×30 min),或多次短时间快走运动(MS)(6次×5 min,每次中间休息30 min)。数据收集后以独立样本t检验和双因素方差分析进行统计检验。研究结果发现:MS在运动后超额摄氧量(EPOC)和恢复期能量消耗显著高于SL,且MS的总摄氧量和总能量消耗(运动期+恢复期)也显著高于SL;而SL在运动结束后甘油浓度显著高于运动前,同时显著高于同期的MS。本研究认为,多次短时间的运动在恢复期的能量消耗显著大于单次长时间的运动,且在恢复期脂肪的消耗也较高,建议不易开展长时间运动的人,可采用多次短时间的运动方式,以增加能量和脂肪的消耗。     

Dual Energy X-Ray Absorptiometry Body Composition Reference Values from NHANES

In 2008 the National Center for Health Statistics released a dual energy x-ray absorptiometry (DXA) whole body dataset from the NHANES population-based sample acquired with modern fan beam scanners in 15 counties across the United States from 1999 through 2004. The NHANES dataset was partitioned by gender and ethnicity and DXA whole body measures of %fat, fat mass/height², lean mass/height², appendicular lean mass/height², %fat trunk/%fat legs ratio, trunk/limb fat mass ratio of fat, bone mineral content (BMC) and bone mineral density (BMD) were analyzed to provide reference values for subjects 8 to 85 years old. DXA reference values for adults were normalized to age; reference values for children included total and sub-total whole body results and were normalized to age, height, or lean mass. We developed an obesity classification scheme by using estabbody mass index (BMI) classification thresholds and prevalences in young adults to generate matching classification thresholds for Fat Mass Index (FMI; fat mass/height²). These reference values should be helpful in the evaluation of a variety of adult and childhood abnormalities involving fat, lean, and bone, for establishing entry criteria into clinical trials, and for other medical, research, and epidemiological uses.     

Total Energy Expenditure and Body Composition in Two Free-Living Sympatric Lemurs

Background

Evolutionary theories that account for the unusual socio-ecological traits and life history features of group-living prosimians, compared with other primates, predict behavioral and physiological mechanisms to conserve energy. Low energy output and possible fattening mechanisms are expected, as either an adaptive response to drastic seasonal fluctuations of food supplies in Madagascar, or persisting traits from previously nocturnal hypometabolic ancestors. Free ranging ring-tailed lemurs (Lemur catta) and brown lemurs (Eulemur sp.) of southern Madagascar have different socio-ecological characteristics which allow a test of these theories: Both gregarious primates have a phytophagous diet but different circadian activity rhythms, degree of arboreality, social systems, and slightly different body size.

Methodology and Results

Daily total energy expenditure and body composition were measured in the field with the doubly labeled water procedure. High body fat content was observed at the end of the rainy season, which supports the notion that individuals need to attain a sufficient physical condition prior to the long dry season. However, ring-tailed lemurs exhibited lower water flux rates and energy expenditure than brown lemurs after controlling for body mass differences. The difference was interpreted to reflect higher efficiency for coping with seasonally low quality foods and water scarcity. Daily energy expenditure of both species was much less than the field metabolic rates predicted by various scaling relationships found across mammals.

Discussion

We argue that low energy output in these species is mainly accounted for by low basal metabolic rate and reflects adaptation to harsh, unpredictable environments. The absence of observed sex differences in body weight, fat content, and daily energy expenditure converge with earlier investigations of physical activity levels in ring-tailed lemurs to suggest the absence of a relationship between energy constraints and the evolution of female dominance over males among lemurs. Nevertheless, additional seasonal data are required to provide a definitive conclusion.     

Obesity in Children: Recent Advances in Energy Metabolism and Body Composition

In this paper we review recent advances in energy metabolism and body composition studies in pre-pubescent children and the relationship to childhood obesity. Our review on energy expenditure focusses on studies of total energy expenditure using doubly labeled water, the role of energy expenditure in the development of obesity, and the determinants of resting energy expenditure in children. The relatively few studies that have examined the regulation of energy and macronutrient intake in children are also reviewed. In terms of body composition, we focus on recent methodological studies that have developed existing techniques for application to the pediatric population, including dual energy X-ray absorptiometry and bioelectrical resistance. Lastly, we review existing information relating to measurement and alteration of body fat distribution in children.     

Difructose Anhydride III Does Not Contribute to Body Energy Accumulation in Rats

We evaluated the body energy accumulation as fat and protein from ingestion of difructose anhydride III (DFAIII). Male Wistar rats were fed 0, 0.25, 0.5, 1.0, or 1.5 g per d of sucrose or DFAIII added to a 7 g of basal diet for 20 d. Supplements of DFAIII did not increase whole body or peripheral fat or total body energy, whereas sucrose increased them in a dose-dependent manner. Dose-dependent increases in body water were observed in both groups. The body protein was influenced by the dose of sugars. The estimated available energy value of DFAIII was 0.263 kcal per gram; this value is one-fifteenth that of sucrose. Ingestion of DFAIII dose-dependently increased the cecal SCFA pool. DFAIII was not detected in feces, showing complete degradation of DFAIII in the intestine. These results indicate that DFAIII is a fermentable saccharide with quite low available energy for fat accumulation.     

Energy Expenditure Determined by Self-Reported Physical Activity Is Related to Body Fatness

BUCHOWSKI, MACIEJ S., KAREN M. TOWNSEND, KONG Y. CHEN, SARI A. ACRA, AND MING SUN. Energy expenditure determined by self-reported physical activity is related to body fatness. Obes. Res. 1999;7:23–33. Objective : Activity self-reports are a commonly used tool in assessing daily physical activity (PA) and associated energy expenditure (EE). This study examined the effect of relative body fatness (%BF) on differences between self-reported and measured duration and associated EE in healthy adults. Research Methods and Procedures: Men and women (n= 115, age 38±9 years), ranging in %BF from 7.9% to 58.9%, spent two separate days (normal and exercise) in a whole-room indirect calorimeter where EE was measured. While in the room calorimeter, subjects reported the type, intensity, and duration of each performed PA. The Compendium of Physical Activity was used to calculate the energy cost of each reported activity. The EE of all self-reported activities (EE_r) was categorized into four intensity levels, synchronized, and compared with EE from the room calorimeter (EE_m). Results : With increasing %BF, subjects significantly overestimated duration of more strenuous activities (≥4.5), while underestimating moderate activities (2.5 to 4.4 metabolic equivalents (METs)). Misreporting of duration and/or intensity caused an overestimation or underestimation of PA-associated EE at these levels. Reported EE sleep was lower than measured EE sleep, although both had similar durations. As a result, total EE_r was similar to EE_m. Discussion : Individual variability of daily total PA and associated EE generated from self-reports in adults is high. Persons with a higher %BF report duration and/or intensity of moderate to high levels of PA with lower accuracy than leaner individuals. We conclude using the Compendium of Physical Activity is not suitable for the accurate estimation of self-reported EE of AA in adults with a higher %BF.     

Influence of Body Composition on the Accuracy of Reported Energy Intake in Children

Objective: Mis‐reporting dietary intake is a substantial barrier to understanding the role of dietary behavior in disease. Work with adults indicates that heavier individuals under‐report dietary intake and that under‐reporting may be macronutrient‐specific. Whether weight status and macronutrient intake influence the accuracy of dietary reports among children, however, is less clear. This research evaluated children's dietary reporting accuracy as a function of their relative weight, body composition, and macronutrient intake. Research Methods and Procedures: Participants included 146 4‐ to 11‐year‐old children. Reported energy intake was determined by interviewing children in the presence of parents, using three multiple pass, 24‐hour recalls. Children were classified as having had an under‐reported, accurately reported, or over‐reported dietary intake relative to total energy expenditure, as measured by doubly labeled water. Reporting accuracy was examined as a function of children's body weight, body composition (using dual energy x‐ray absorptiometry), and macronutrient intake. Results: Average reported intake was, on average, 14% greater than children's estimated expenditure (p < 0.01). Reporting accuracy varied as a function of children's relative weight and body composition; under‐reporting tended to occur among heavier children, having the highest body fat content (p < 0.0001) and relative weight (p < 0.0001). Discussion: These findings suggest that weight status influences the accuracy of dietary reports made by children and their parents. More research is needed to address possible psychological and social factors that introduce bias in reporting children's dietary data.     

Role of Stearoyl-CoA Desaturase-1 in Skin Integrity and Whole Body Energy Balance

The skin is the single largest organ in humans, serving as a major barrier to infection, water loss, and abrasion. The functional diversity of skin requires the synthesis of large amounts of lipids, such as triglycerides, wax esters, squalene, ceramides, free cholesterol, free fatty acids, and cholesterol and retinyl esters. Some of these lipids are used as cell membrane components, signaling molecules, and a source of energy. An important class of lipid metabolism enzymes expressed in skin is the Δ⁹-desaturases, which catalyze the synthesis in Δ⁹-monounsaturated lipids, primarily oleoyl-CoA (18:1n-9) and palmitoyl-CoA (16:1n-7), the major monounsaturated fatty acids in cutaneous lipids. Mice with a deletion of the Δ⁹-desaturase-1 isoform (SCD1) either globally (Scd1^−/−) or specifically in the skin (skin-specific Scd1-knockout; SKO) present with marked changes in cutaneous lipids and skin integrity. Interestingly, these mice also exhibit increased whole body energy expenditure, protection against diet-induced adiposity, hepatic steatosis, and glucose intolerance. The increased energy expenditure in skin-specific Scd1-knockout (SKO) mice is a surprising phenotype, as it links cutaneous lipid homeostasis with whole body energy balance. This minireview summarizes the role of skin SCD1 in regulating skin integrity and whole body energy homeostasis and offers a discussion of potential pathways that may connect these seemingly disparate phenotypes.     

Protein Body Composition in Cuburbita maxima Cotyledons as Determined by Energy Dispersive X-Ray Analysis

Energy dispersive x-ray analysis was used to study the composition of certain protein body components in Cucurbita maxima cotyledons. The globoid crystal was rich in phosphorus, potassium, and magnesium. This elemental composition provides further evidence that the globoid crystal in squash cotyledon protein bodies is composed of phytin, a myoinositol hexaphosphoric acid salt of potassium and magnesium. Calcium, a common component of phytin in many species, was absent or present in only trace amounts in the globoid crystals of squash. Results of analyses of globoid crystals from seeds produced in different parts of North America suggest that there is definite specificity for the cations used in phytin deposition. Variations in soil types and other environmental factors seem not to have influenced the type of cation stored. Energy dispersive x-ray analysis of the proteinaceous regions revealed the presence of phosphorus, sulfur, and a trace of chlorine. Sulfur was expected, due to the presence of some sulfur containing amino acids in the protein.     

Reduced Body Weight and Increased Energy Expenditure in Transgenic Mice Over-Expressing Soluble Leptin Receptor

Background

Soluble leptin receptor (OBRe), one of several leptin receptor isoforms, is the only bona fide leptin binding protein in plasma. Our earlier studies demonstrated that OBRe modulates leptin levels in circulation. Both clinical and in vitro studies have shown that OBRe expression is inversely correlated to body weight and leptin levels. However, it is not clear whether OBRe plays an active role, either in collaboration with leptin or independently, in the maintenance of body weight.

Methodology/Principal Findings

To investigate the function of OBRe in the regulation of energy homeostasis, we generated transgenic mice that express OBRe under the control of human serum amyloid P (hSAP) component gene promoter. The transgene led to approximately doubling of OBRe in circulation in the transgenic mice than in wild type control mice. Transgenic mice exhibited lower body weight at 4 weeks of age, and slower rate of weight gain when compared with control mice. Furthermore, transgenic mice had lower body fat content. Indirect calorimetry revealed that transgenic mice had reduced food intake, increased basal metabolic rate, and increased lipid oxidation, which could account for the differences in body weight and body fat content. Transgenic mice also showed higher total circulating leptin, with the majority of it being in the bound form, while the amount of free leptin is comparable between transgenic and control mice.

Conclusions

These results are consistent with the role of OBRe as a leptin binding protein in regulating leptin''s bioavailability and activity.     

横断山区高山姬鼠身体能值的适应性调节

为探讨栖息于横断山地区高山姬鼠(Apodemus cheurieri)身体状况与环境之间的适应关系,对野外和实验室条件下高山姬鼠的身体能值进行了测定.结果表明,高山姬鼠身体能值存在季节性变化,6月最高,9月次之,11月开始下降,到次年3月达到最低.冷驯化条件下,其身体能值显著降低.高山姬鼠的身体能值在不同季节和冷驯化条件下表现出的变化模式,与其低纬度高海拔、年平均温度较低的生存环境有关.反映了横断山区小型哺乳动物在季节性环境中的生存机制和适应对策.     

Muscles, Elastic Energy, and the Dynamics of Body Stiffness in Swimming Eels

SYNOPSIS. TO investigate the capacity of the myomeric musclesto actively change the stiffness of the body during bending,mid-caudal sections (spanning two to three intervertebral joints)of intact, freshly-killed American eels, Anguilla rostrata,were dynamically bent (3 Hz,+min;4% maximal muscle strain) usingthe whole-body workloop technique. Following unstimulated cycles,the left- and right-sides of the musculature were alternatelystimulated at supra-maximal voltages and at eight differentphases relative to the strain cycle of the muscle. The body'sflexural stiffness (Nm2) increased maximally by a factor ofthree relative to that when the muscles were unstimulated. Thenet external work (J kg^–1) needed to bend the body decreasedmaximally by a factor of seven relative to that when the muscleswere unstimulated. Both of these mechanical features variedsinusoidally with changes in the phase of the stimulus. Stimulusphase of caudal muscle in live swimming eels, taken from otherstudies, leads to the prediction that the caudal muscles increasebody stiffness and produce net positive mechanical work simultaneouslyduring steady forward swimming. The association of increasedbody stiffness and net positive muscle work, and the occurrenceof maximal net muscle power output at a stimulus phase of 325°(as the muscle segment lengthens), suggests that net positivepower is produced, in part, using an elastic strain energy mechanism.     

横断山区大绒鼠体重和身体能值的季节变化

为研究栖息于横断山地区的大绒鼠(Eothenomys miletus)身体状况与环境之间的适应关系,本实验对野外、实验室饲养及冷驯化条件下大绒鼠的体重和身体能值进行了测定.结果表明,大绒鼠体重及身体能值存在季节性变化,大绒鼠体重及身体能值的平均值3月最低,6月最高,9月次之,11月开始下降.冷驯化条件下大绒鼠的体重和身体能值均显著低于实验室饲养条件下的,说明在季节变化过程中温度可能是影响其体重和身体能值的一个重要因素.大绒鼠的体重和身体能值的季节变化模式与横断山区的特殊生存环境有关,在一定程度上反映了该物种对横断山特殊环境的生存适应对策.