Hormone-Sensitive Lipase Knockouts

All treatments for obesity, including dietary restriction of carbohydrates, have a goal of reducing the storage of fat in adipocytes. The chief enzyme responsible for the mobilization of FFA from adipose tissue, i.e., lipolysis, is thought to be hormone-sensitive lipase (HSL). Studies of HSL knockouts have provided important insights into the functional significance of HSL and into adipose metabolism in general. Studies have provided evidence that HSL, though possessing triacylglycerol lipase activity, appears to be the rate-limiting enzyme for cholesteryl ester and diacylglycerol hydrolysis in adipose tissue and is essential for complete hormone stimulated lipolysis, but other triacylglycerol lipases are important in mediating triacylglycerol hydrolysis in lipolysis. HSL knockouts are resistant to both high fat diet-induced and genetic obesity, displaying reduced quantities of white with increased amounts of brown adipose tissue, increased numbers of adipose macrophages, and have multiple alterations in the expression of genes involved in adipose differentiation, including transcription factors, markers of adipocyte differentiation, and enzymes of fatty acid and triglyceride synthesis. With disruption of lipolysis by removal of HSL, there is a drastic reduction in lipogenesis and alteration in adipose metabolism

A falls prevention programme to improve quality of life, physical function and falls efficacy in older people receiving home help services: study protocol for a randomised controlled trial

BACKGROUND: Falls and fall-related injuries in older adults are associated with great burdens, both for the individuals, the health care system and the society. Previous research has shown evidence for the efficiency of exercise as falls prevention. An understudied group are older adults receiving home help services, and the effect of a falls prevention programme on health-related quality of life is unclear. The primary aim of this randomised controlled trial is to examine the effect of a falls prevention programme on quality of life, physical function and falls efficacy in older adults receiving home help services. A secondary aim is to explore the mediating factors between falls prevention and health-related quality of life. METHODS: The study is a single-blinded randomised controlled trial. Participants are older adults, aged 67 or older, receiving home help services, who are able to walk with or without walking aids, who have experienced at least one fall during the last 12 months and who have a Mini Mental State Examination of 23 or above. The intervention group receives a programme, based on the Otago Exercise Programme, lasting 12 weeks including home visits and motivational telephone calls. The control group receives usual care. The primary outcome is health-related quality of life (SF-36). Secondary outcomes are leg strength, balance, walking speed, walking habits, activities of daily living, nutritional status and falls efficacy. All measurements are performed at baseline, following intervention at 3 months and at 6 months' follow-up. Sample size, based on the primary outcome, is set to 150 participants randomised into the two arms, including an estimated 15-20% drop out. Participants are recruited from six municipalities in Norway. DISCUSSION: This trial will generate new knowledge on the effects of an exercise falls prevention programme among older fallers receiving home help services. This knowledge will be useful for clinicians, for health managers in the primary health care service and for policy makers

Nutrition education: a questionnaire for assessment and teaching

It is generally recognized that there is a need for improved teaching of nutrition in medical schools and for increased education of the general population. A questionnaire, derived in part from a study of physician knowledge, was administered to first year medical students in order to assess their knowledge of various aspects of nutrition and metabolism, and as a teaching tool to transmit information about the subject. The performance of first year students was consistent with a generally educated population but there were surprising deficits in some fundamental areas of nutrition. Results of the questionnaire are informative about student knowledge, and immediate reinforcement from a questionnaire may provide a useful teaching tool. In addition, some of the subject matter can serve as a springboard for discussion of critical issues in nutrition such as obesity and markers for cardiovascular disease. A major barrier to improved teaching of nutrition is the lack of agreement on some of these critical issues and there are apparent inconsistencies in recommendations of government and health agencies. It seems reasonable that improved teaching should address the lack of knowledge of nutrition, rather than knowledge of official guidelines. Student awareness of factual information should be the primary goal

ApoB100-LDL Acts as a Metabolic Signal from Liver to Peripheral Fat Causing Inhibition of Lipolysis in Adipocytes

International audienceBACKGROUND: Free fatty acids released from adipose tissue affect the synthesis of apolipoprotein B-containing lipoproteins and glucose metabolism in the liver. Whether there also exists a reciprocal metabolic arm affecting energy metabolism in white adipose tissue is unknown. METHODS AND FINDINGS: We investigated the effects of apoB-containing lipoproteins on catecholamine-induced lipolysis in adipocytes from subcutaneous fat cells of obese but otherwise healthy men, fat pads from mice with plasma lipoproteins containing high or intermediate levels of apoB100 or no apoB100, primary cultured adipocytes, and 3T3-L1 cells. In subcutaneous fat cells, the rate of lipolysis was inversely related to plasma apoB levels. In human primary adipocytes, LDL inhibited lipolysis in a concentration-dependent fashion. In contrast, VLDL had no effect. Lipolysis was increased in fat pads from mice lacking plasma apoB100, reduced in apoB100-only mice, and intermediate in wild-type mice. Mice lacking apoB100 also had higher oxygen consumption and lipid oxidation. In 3T3-L1 cells, apoB100-containing lipoproteins inhibited lipolysis in a dose-dependent fashion, but lipoproteins containing apoB48 had no effect. ApoB100-LDL mediated inhibition of lipolysis was abolished in fat pads of mice deficient in the LDL receptor (Ldlr(-/-)Apob(100/100)). CONCLUSIONS: Our results show that the binding of apoB100-LDL to adipocytes via the LDL receptor inhibits intracellular noradrenaline-induced lipolysis in adipocytes. Thus, apoB100-LDL is a novel signaling molecule from the liver to peripheral fat deposits that may be an important link between atherogenic dyslipidemias and facets of the metabolic syndrome

Relationships between cardiorespiratory fitness/muscular strength and 18F-fluorodeoxyglucose uptake in brown adipose tissue after exposure to cold in young, sedentary adults

Humans have metabolically active brown adipose tissue (BAT). However, what is the relation between exercise or physical activity with this tissue remains controversial. Therefore, the main aim of the present study is to examine whether cardiorespiratory fitness and muscular strength are associated with brown adipose tissue (BAT) volume and activity after exposure to cold in young, sedentary adults. Cardiorespiratory fitness was determined in 119 young, healthy, sedentary adults (68% women, age 21.9 ± 2.1 years, body mass index 25 ± 4.8 kg/m2) via the maximum treadmill exercise test, and their muscular strength assessed by the handgrip strength test and the 1-repetition maximum bench and leg press tests. Some days later, all subjects were exposed to 2 h of personalized exposure to cold and their cold-induced BAT volume and activity determined by a combination of 18F-fluorodeoxyglucose (18F-FDG) positron emission tomography and computed tomography scan. Cardiorespiratory fitness was associated with neither the BAT volume nor BAT activity (P ≥ 0.05). However, handgrip strength with respect to lean body mass was positively (though weakly) associated with BAT activity as represented by the 18F-FDG mean standardised uptake value (SUV) (β = 3.595, R2 = 0.039, P = 0.031) and SUVpeak value (β = 15.314, R2 = 0.037, P = 0.035). The above relationships remained after adjusting for several confounders. No other associations were found. Handgrip strength with respect to lean body mass is positively associated with BAT activity (SUVmean and SUVpeak) in young adults after exposure to cold - but only weakly. Further studies are needed to reveal the relationship between muscular fitness and human BAT characteristics.This study was supported by the Spanish Ministry of Economy and Competitiveness via the Fondo de Investigación Sanitaria del Instituto de Salud Carlos III (PI13/01393), Retos de la Sociedad (DEP2016-79512-R) and European Regional Development Funds (ERDF), the Spanish Ministry of Education (FPU13/04365 and FPU14/04172), the Fundación Iberoamericana de Nutrición (FINUT), the Redes Temáticas de Investigación Cooperativa RETIC (Red SAMID RD16/0022), the AstraZeneca HealthCare Foundation, the University of Granada Plan Propio de Investigación 2016 -Excellence actions: Unit of Excellence on Exercise and Health (UCEES) - and Plan Propio de Investigación 2018 - Programa Contratos-Puente, and the Junta de Andalucía, Consejería de Conocimiento, Investigación y Universidades (ERDF: SOMM17/6107/UGR)

Increasing Protein at the Expense of Carbohydrate in the Diet Down-Regulates Glucose Utilization as Glucose Sparing Effect in Rats

High protein (HP) diet could serve as a good strategy against obesity, provoking the changes in energy metabolic pathways. However, those modifications differ during a dietary adaptation. To better understand the mechanisms involved in effect of high protein diet (HP) on limiting adiposity in rats we studied in parallel the gene expression of enzymes involved in protein and energy metabolism and the profiles of nutrients oxidation. Eighty male Wistar rats were fed a normal protein diet (NP, 14% of protein) for one week, then either maintained on NP diet or assigned to a HP diet (50% of protein) for 1, 3, 6 and 14 days. mRNA levels of genes involved in carbohydrate and lipid metabolism were measured in liver, adipose tissues, kidney and muscles by real time PCR. Energy expenditure (EE) and substrate oxidation were measured by indirect calorimetry. Liver glycogen and plasma glucose and hormones were assayed. In liver, HP feeding 1) decreased mRNA encoding glycolysis enzymes (GK, L-PK) and lipogenesis enzymes(ACC, FAS), 2) increased mRNA encoding gluconeogenesis enzymes (PEPCK), 3) first lowered, then restored mRNA encoding glycogen synthesis enzyme (GS), 4) did not change mRNA encoding β-oxidation enzymes (CPT1, ACOX1, βHAD). Few changes were seen in other organs. In parallel, indirect calorimetry confirmed that following HP feeding, glucose oxidation was reduced and fat oxidation was stable, except during the 1st day of adaptation where lipid oxidation was increased. Finally, this study showed that plasma insulin was lowered and hepatic glucose uptake was decreased. Taken together, these results demonstrate that following HP feeding, CHO utilization was increased above the increase in carbohydrate intake while lipogenesis was decreased thus giving a potential explanation for the fat lowering effect of HP diets

A Functional Misexpression Screen Uncovers a Role for Enabled in Progressive Neurodegeneration

Drosophila is a well-established model to study the molecular basis of neurodegenerative diseases. We carried out a misexpression screen to identify genes involved in neurodegeneration examining locomotor behavior in young and aged flies. We hypothesized that a progressive loss of rhythmic activity could reveal novel genes involved in neurodegenerative mechanisms. One of the interesting candidates showing progressive arrhythmicity has reduced enabled (ena) levels. ena down-regulation gave rise to progressive vacuolization in specific regions of the adult brain. Abnormal staining of pre-synaptic markers such as cystein string protein (CSP) suggest that axonal transport could underlie the neurodegeneration observed in the mutant. Reduced ena levels correlated with increased apoptosis, which could be rescued in the presence of p35, a general Caspase inhibitor. Thus, this mutant recapitulates two important features of human neurodegenerative diseases, i.e., vulnerability of certain neuronal populations and progressive degeneration, offering a unique scenario in which to unravel the specific mechanisms in an easily tractable organism

Nonequilibrium thermodynamics and energy efficiency in weight loss diets

Carbohydrate restriction as a strategy for control of obesity is based on two effects: a behavioral effect, spontaneous reduction in caloric intake and a metabolic effect, an apparent reduction in energy efficiency, greater weight loss per calorie consumed. Variable energy efficiency is established in many contexts (hormonal imbalance, weight regain and knock-out experiments in animal models), but in the area of the effect of macronutrient composition on weight loss, controversy remains. Resistance to the idea comes from a perception that variable weight loss on isocaloric diets would somehow violate the laws of thermodynamics, that is, only caloric intake is important ("a calorie is a calorie"). Previous explanations of how the phenomenon occurs, based on equilibrium thermodynamics, emphasized the inefficiencies introduced by substrate cycling and requirements for increased gluconeogenesis. Living systems, however, are maintained far from equilibrium, and metabolism is controlled by the regulation of the rates of enzymatic reactions. The principles of nonequilibrium thermodynamics which emphasize kinetic fluxes as well as thermodynamic forces should therefore also be considered