The links between membrane composition, metabolic rate and lifespan

The acyl composition of tissue phospholipids varies in a systematic manner among species. Phospholipids, and thus membrane bilayers, from the tissues of small mammal and bird species have a high content of docosahexaenoic acid (DHA) compared to large species. A similar difference exists between the tissues of endothermic mammals and ectothermic reptiles. High DHA content in phospholipids is associated with high metabolic activity and this observation has led to the development of the "membrane pacemaker" theory of metabolism. This proposes that highly polyunsaturated acyl chains impart physical properties to membrane bilayers that enhance and speed up the molecular activity of membrane proteins and consequently the metabolic activity of cells, tissues and the whole animal. The brain has highly polyunsaturated membranes irrespective of body size and possible reasons for this are discussed. Highly polyunsaturated acyl chains are very susceptible to peroxidative damage. It is suggested that these chemical properties of highly polyunsaturated membrane acyl chains have important implications for understanding aging and the determination of longevity.     

Complex links between dietary lipids, endogenous endotoxins and metabolic inflammation

Metabolic diseases such as obesity are characterized by a subclinical inflammatory state that contributes to the development of insulin resistance and atherosclerosis. Recent reports also indicate that (i) there are alterations of the intestinal microbiota in metabolic diseases and (ii) absorption of endogenous endotoxins (namely lipopolysaccharides, LPS) can occur, particularly during the digestion of lipids. The aim of the present review is to highlight recently gained knowledge regarding the links between high fat diets, lipid digestion, intestinal microbiota and metabolic endotoxemia & inflammation.     

Basal metabolic rate: history, composition, regulation, and usefulness

The concept of basal metabolic rate (BMR) was developed to compare the metabolic rate of animals and initially was important in a clinical context as a means of determining thyroid status of humans. It was also important in defining the allometric relationship between body mass and metabolic rate of mammals. The BMR of mammals varies with body mass, with the same allometric exponent as field metabolic rate and with many physiological and biochemical rates. The membrane pacemaker theory proposes that the fatty acid composition of membrane bilayers is an important determinant of a species BMR. In both mammals and birds, membrane polyunsaturation decreases and monounsaturation increases with increasing body mass and a decrease in mass-specific BMR. The secretion and production of thyroid hormones in mammals are related to body mass, with the allometric exponent similar to BMR; yet there is no body size-related variation in either total or free concentrations of thyroid hormones in plasma of mammals. It is suggested that in different-sized mammals, the secretion/production of thyroid hormones is a result of BMR differences rather than their cause. BMR is a useful concept in some situations but not in others.     

Genetic links between diet and lifespan: shared mechanisms from yeast to humans

Caloric restriction is the only known non-genetic intervention that robustly extends lifespan in mammals. This regimen also attenuates the incidence and progression of many age-dependent pathologies. Understanding the genetic mechanisms that underlie dietary-restriction-induced longevity would therefore have profound implications for future medical treatments aimed at tackling conditions that are associated with the ageing process. Until recently, however, almost nothing was known about these mechanisms in metazoans. Recent advances in our understanding of the genetic bases of energy sensing and lifespan control in yeast, invertebrates and mammals have begun to solve this puzzle. Evidence is mounting that the brain has a crucial role in sensing dietary restriction and promoting longevity in metazoans.     

The protein-mediated transfer of phosphatidylcholine between membranes. The effect of membrane lipid composition and ionic composition of the medium.

The phosphatidylcholine exchange protein from bovine liver catalyzes the transfer of phosphatidylcholine between rat liver mitochondria and sonicated liposomes. The effect of changes in the liposomal lipid composition and ionic composition of the medium on the transfer have been determined. In addition, it has been determined how these changes affected the electrophoretic mobility i.e. the surface charge of the membrane particles involved. Transfer was inhibited by the incorporation of negatively charged phosphatidic acid, phosphatidylserine, phosphatidylglycerol and phosphatidylinositol into the phosphatidylcholine-containing vesicles; zwitterionic phosphatidyl-ethanolamine had much less of an inhibitory effect while positively charged stearylamine stimulated. The cation Mg2+ and, to a lesser extent, K+ overcame the inhibitory effect exerted by phosphatidic acid, in that concentration range where these ions neutralized the negative surface charge most effectively. Under conditions where Mg2+ and K+ affected the membrane surface charge relatively little inhibition was observed. In measuring the protein-mediated transfer between a monolayer and vesicles consisting of only phosphatidylcholine, cations inhibited the transfer in the order La3+ greater than Mg2+ larger than or equal to Ca2+ greater than K+ = Na+. Inhibition was not related to the ionic strength, and very likely reflects an interference of these cations with an electrostatic interaction between the exchange protein and the polar head group of phosphatidylcholine.     

The correlation between biofilm biopolymer composition and membrane fouling in submerged membrane bioreactors

Biofouling, the combined effect of microorganism and biopolymer accumulation, significantly reduces the process efficiency of membrane bioreactors (MBRs). Here, four biofilm components, alpha-polysaccharides, beta-polysaccharides, proteins and microorganisms, were quantified in MBRs. The biomass of each component was positively correlated with the transmembrane pressure increase in MBRs. Proteins were the most abundant biopolymer in biofilms and showed the fastest rate of increase. The spatial distribution and co-localization analysis of the biofouling components indicated at least 60% of the extracellular polysaccharide (EPS) components were associated with the microbial cells when the transmembrane pressure (TMP) entered the jump phase, suggesting that the EPS components were either secreted by the biofilm cells or that the deposition of these components facilitated biofilm formation. It is suggested that biofilm formation and the accumulation of EPS are intrinsically coupled, resulting in biofouling and loss of system performance. Therefore, strategies that control biofilm formation on membranes may result in a significant improvement of MBR performance.     

Body mass, body composition and sleeping metabolic rate before, during and after endurance training

Metabolic rate, more specifically resting metabolic rate (RMR) or sleeping metabolic rate (SMR), of an adult subject is usually expressed as a function of the fat-free mass (FFM). Chronic exercise is thought to increase FFM and thus to increase RMR and SMR. We determined body mass (BM), body composition, and SMR before, during, and after an endurance training programme without interfering with energy intake. The subjects were 11 women and 12 men, aged 37 (SD 3) years and body mass index 22.3 (SD 1.5) kg · m^–2. The endurance training prepared subjects to run a half marathon competition after 44 weeks. The SMR was measured overnight in a respiration chamber. Body composition was measured by hydrostatic weighing. Measurements were performed at 0, 8, 20, 40, and 90 weeks after the start of the training. The BM had decreased from a mean value of 66.6 (SD 6.9) to 65.6 (SD 6.7) kg (P<0.01), fat mass (FM) had decreased from 17.1 (SD 3.9) to 13.5 (SD 3.6) kg (P<0.001), and FFM had increased from 49.5 (SD 7.3) to 52.2 (SD 7.6) kg (P<0.001) at 40 weeks. Mean SMR before and after 40 weeks training was 6.5 (SD 0.7) and 6.2 (SD 0.6) MJ · day^–1 (P<0.05). The decrease in SMR was related to the decrease in BM (r=0.62,P=0.001). At 90 weeks, when most subjects had not trained for nearly a year, BM and SMR were not significantly different from the initial value while FM and FFM had not changed since week 40 of training. In conclusion, it was found that an exercise induced increase in FFM did not result in an increase in SMR. There was an indication of the opposite effect, a decrease in SMR in the long term during training, possibly as a defence mechanism of the body in the maintenance of BM.     

The intraspecies relationship between tissue turnover and metabolic rate in rats

Ecologists interested in studying fluctuating relationships between consumers and nutrient sources are increasingly involved in modeling the rate at which consumers incorporate dietary components. In mammals a correlation between resting metabolic rate (RMR) and tissue turnover may exist across a range of species. Less is known about the variation of tissue turnover rate within a species, and how that correlates with RMR. Here we examine two strains of rats (Rattus norvegicus) with different RMR to test whether variation in RMR is positively correlated with tissue turnover rate within a species. If RMR, a relatively simple measurement, can be correlated with tissue turnover, then this relationship could be used to better interpret ecological functions, including impact of migratory or seasonally available nutrient sources. Here, the changing isotope signature in rat whole blood was modeled using a modified exponential decay equation and a reaction progress variable model. The modeled rate of turnover, metabolic rate (O₂ consumed), and mass were then compared between strains of rats. The mass and RMRs (conditions during which RMRs were determined modified from the ideal, as outlined in the Methods) were significantly different between strains, but half-life and the metabolic tissue replacement component of turnover (as opposed to turnover from mass gain) were not. No significant correlation was found between RMR and metabolic tissue replacement between the strains. Results suggest that within a species showing a range of RMRs, blood tissue turnover should not vary significantly.     

Familial resemblance of body composition,physical activity,and resting metabolic rate in pre-school children

Background:

Although parental obesity is a well-established predisposing factor for the development of obesity, associations between regional body compositions, resting metabolic rates (RMR), and physical activity (PA) of parents and their pre-school children remain unknown. The objective of this study was to investigate parent-child correlations for total and regional body compositions, resting energy expenditures, and physical activity.

Methods:

Participants were 89 children aged 2-6 years and their parents, consisting of 61 families. Resting metabolic rate was assessed using indirect calorimetry. Total and regional body compositions were measured by both dual energy X-ray absorptiometry (DXA) and deuterium dilution. Physical activity was assessed by an accelerometer.

Results:

There was a significant parent-offspring regression for total fat free mass (FFM) between children and their mothers (P=0.02), fathers (P=0.02), and mid-parent (average of father and mother value) (P=0.002) when measured by DXA. The same was true for fat mass (FM) between children and mothers (P<0.01), fathers (P=0.02), and mid-parent (P=0.001). There was no significant association between children and parents for physical activity during the entire week, weekend, weekdays, and different parts of days, except for morning activity, which was positively related to the mothers’ morning activities (P<0.01) and mid-parent (P=0.009). No association was found between RMR of children and parents before and after correction for FFM and FM.

Conclusion:

These data suggest a familial resemblance for total body composition between children and their parents. Our data showed no familial resemblance for PA and RMR between children and their parents. Key Words: Obesity, Familial resemblance, Children, Resting metabolic rate, Physical activity     

Dietary composition specifies consumption, obesity, and lifespan in Drosophila melanogaster

The inability to properly balance energy intake and expenditure with nutrient supply forms the basis for some of today's most pressing health issues, including diabetes and obesity. Mechanisms of nutrient homeostasis may also lie at the root of dietary restriction, a manipulation whereby reduced nutrient availability extends lifespan and ameliorates age-related deteriorations in many species. The traditional belief that the most important aspect of the diet is its energetic (i.e. caloric) content is currently under scrutiny. Hypotheses that focus on diet composition and highlight more subtle characteristics are beginning to emerge. Using Drosophila melanogaster , we asked whether diet composition alone, independent of its caloric content, was sufficient to impact behavior, physiology, and lifespan. We found that providing flies with a yeast-rich diet produced lean, reproductively competent animals with reduced feeding rates. Excess dietary sugar, on the other hand, promoted obesity, which was magnified during aging. Addition of dietary yeast often limited or reversed the phenotypic changes associated with increased dietary sugar and vice versa, and dietary imbalance was associated with reduced lifespan. Our data reveal that diet composition, alone and in combination with overall caloric intake, modulates lifespan, consumption, and fat deposition in flies, and they provide a useful foundation for dissecting the underlying genetic mechanisms that link specific nutrients with important aspects of general health and longevity.     

The interaction between metabolic rate,habitat choice,and resource use in a polymorphic freshwater species

1. Resource polymorphism is common across taxa and can result in alternate ecotypes with specific morphologies, feeding modes, and behaviors that increase performance in a specific habitat. This can result in high intraspecific variation in the expression of specific traits and the extent to which these traits are correlated within a single population. Although metabolic rate influences resource acquisition and the overall pace of life of individuals it is not clear how metabolic rate interacts with the larger suite of traits to ultimately determine individual fitness.
2. We examined the relationship between metabolic rates and the major differences (habitat use, morphology, and resource use) between littoral and pelagic ecotypes of European perch (Perca fluviatilis) from a single lake in Central Sweden.
3. Standard metabolic rate (SMR) was significantly higher in pelagic perch but did not correlate with resource use or morphology. Maximum metabolic rate (MMR) was not correlated with any of our explanatory variables or with SMR. Aerobic scope (AS) showed the same pattern as SMR, differing across habitats, but contrary to expectations, was lower in pelagic perch.
4. This study helps to establish a framework for future experiments further exploring the drivers of intraspecific differences in metabolism. In addition, since metabolic rates scale with temperature and determine predator energy requirements, our observed differences in SMR across habitats will help determine ecotype‐specific vulnerabilities to climate change and differences in top‐down predation pressure across habitats.

     

Osh6 links yeast vacuolar functions to lifespan extension and TOR

Comment on: Gebre S, et al. Cell Cycle 2012; 11:2176-88.Almost all organisms age–the aging process is both genetically determined and can be modified by the environment. Lifespan extension by dietary restriction (DR) is observed in evolutionarily distant species from yeast to mammals. Not only are the phenomena of aging and DR conserved, but at least some mechanisms and genes are evolutionarily conserved, which may pave the way to manipulate human aging.¹ For example, TOR (target of rapamycin) mediates aging and, when suppressed, triggers anti-aging processes in many species. Moreover, identifying genes that modulate the potential for cell division is of great interest, given that changes in the number of times that cells divide have been associated with longevity manipulations in mammals (including DR).²Sterols are hydrophobic molecules present in all cellular organisms. For instance, cholesterol is an essential structural component of cellular membranes of mammals and several of its derivates have additional hormonal and signaling functions. Oxysterols are oxygenated derivates of cholesterol. Oxysterol-binding protein (OSBP)-related protein (ORP) family members are present in numerous copies from yeast to man, suggesting that this protein family has fundamental functions in eukaryotes. OSBP and ORPs regulate lipid metabolism, vesicle transport and various signaling pathways³ and may specifically mediate lipid exchange at membrane contact sites.The lifespan-extending effect of DR has often been shown to be mediated by specific genes and to be accompanied by discrete changes in gene expression as well as metabolic reprogramming. Both lipid metabolism and cellular recycling activities have been demonstrated to be essential for lifespan extension in numerous species. For example, DR suppresses sterol synthesis from yeast to mammals,⁴ while it induces some form of autophagy, a mighty housekeeping mechanism utilizing lysosomes within its power to recycle various kinds of molecules and cellular structures. Vacuoles, the yeast equivalent of mammalian lysosomes, are highly dynamic organelles that fuse and divide in response to environmental or intrinsic cues. Mutants with defects in vacuolar fusion (such as ypt7Δ, nyv1Δ, vac8Δ, or erg6Δ) are either short-lived or do not appear to respond to DR.⁵While mammals have 12 OSBPs, the yeast genome encodes seven oxysterol-binding protein sequence homologs (OSH). Deletion of any OSH gene alone does not impact on vacuolar morphology, yet deletion of all results in highly fragmented vacuoles, a sign of defective vacuole fusion. Gebre et al. now show that overexpression of OSH family member OSH6 in yeast can complement the vacuole fusion defect of nyv1Δ but not erg6Δ or vac8Δ. Thus, Osh6 mediates vacuolar fusion, which depends on ergosterol (Erg6), and the protein anchor Vac8. In contrast, overexpression of another OSH-family member, OSH5, exacerbated fragmentation and decreased lifespan in wild-type cells. It is interesting to note that OSH5 expression progressively increases with age, and Osh6 overexpression blocked this age-dependent change in OSH5 levels. Also, elevated Osh6 maintains the enrichment of Vac8 in microdomains of vacuolar membranes with advancing age, which is required for vacuole fusion. Intriguingly, exactly at the age when the longevity protein Sir2 declines, Osh6 protein levels also decline.⁶Furthermore, Gebre et al. showed that P_ERG6-OSH6 (ERG6 promoter driving OSH6 overexpression) dramatically extends the lifespan of wild-type and nyv1Δ mutants. tor1Δ mutants are also long-lived, though not so long as P_ERG6-OSH6. Surprisingly, P_ERG6-OSH6 tor1Δ double mutant had a very short lifespan. P_ERG6-OSH6 mutants were more sensitive to TOR inhibitors, indicating that TOR is less active in this strain.⁶ OSH6 overexpression downregulates total cellular sterol levels, just like DR. Osh6 binds PI3P and PI(3,5)P2 which are vacuole-specific lipids.⁷ As such, Osh6 might promote vacuole fusion by regulating the transports and/or distribution of sterols to the vacuolar membranes. But where are the sterols coming from? Numerous overexpression mutants with effects in vacuolar morphology are involved in endocytosis.⁸ Similarly, Osh6’s coiled-coil domain interacts with Vps4, which is located in endosomes. TOR complex 1 (TORC1) also sits on endosomes as well as on vacuoles and actively catalyzes vacuolar scission.⁹ Osh6 may therefore (1) transport sterols from late endosomes to the vacuolar membrane (Fig. 1), which increases the homototypic fusion ability of vacuoles, and (2) averaging the lipids between late endosome and vacuoles promotes also late-endosome-to-vacuole fusion.Open in a separate windowFigure 1. Putative mechanism of the lifespan extension conferred by Osh6 overexpression. TORC1 promotes vacuolar scission and therefore fragments vacuoles. In contrast, Osh6 enhances vacuolar fusion and might be doing this by transporting sterols from the endosomes to the vacuolar membrane. Improved vacuolar morphology then promotes autophagy. Thus, Osh6 appears to counteract TORC1 activity.Overall, Gebre and colleagues link the vacuole to lifespan extension, perhaps via TOR, and reveal that vacuole fusion is both necessary and sufficient for lifespan extension.     

Osh6 links yeast vacuolar functions to lifespan extension and TOR

Comment on: Gebre S, et al. Cell Cycle 2012; 11:2176-88.     

Setting the pace of life: membrane composition of flight muscle varies with metabolic rate of hovering orchid bees

Patterns of metabolic rate variation have been documented extensively in animals, but their functional basis remains elusive. The membrane pacemaker hypothesis proposes that the relative abundance of polyunsaturated fatty acids in membrane phospholipids sets the metabolic rate of organisms. Using species of tropical orchid bees spanning a 16-fold range in body size, we show that the flight muscles of smaller bees have more linoleate (%18 : 3) and stearate (%18 : 0), but less oleate (%18 : 1). More importantly, flight metabolic rate (FlightMR) varies with the relative abundance of 18 : 3 according to the predictions of the membrane pacemaker hypothesis. Although this relationship was found across large differences in metabolic rate, a direct association could not be detected when taking phylogeny and body mass into account. Higher FlightMR, however, was related to lower %16 : 0, independent of phylogeny and body mass. Therefore, this study shows that flight muscle membrane composition plays a significant role in explaining diversity in FlightMR, but that body mass and phylogeny are other factors contributing to their variation. Multiple factors are at play to modulate metabolic capacity, and changing membrane composition can have gradual and stepwise effects to achieve a new range of metabolic rates. Orchid bees illustrate the correlated evolution between membrane composition and metabolic rate, supporting the functional link proposed in the membrane pacemaker hypothesis.     

Accuracy of predicted resting metabolic rate and relationship between resting metabolic rate and cardiorespiratory fitness in obese men

[Purpose]

The purpose of this study is to examine that not only the relationship of the resting metabolic rate (RMR) and cardiorespiratory fitness(VO2peak), but also the comparison between measured and predicted results of RMR in obese men.

[Methods]

60 obese men (body fat>32%) were recruited for this study. They did not participate in regular exercising programs at least 6 months. The RMR was measured with indirect calorimetry and predicted RMR using Herris-Benedicte equation. The cardiorespiratory fitness was determined by directly measuring the oxygen consumption (VO2peak) during the exercise on the treadmill.

[Results]

The significance for the difference between the measured results and predicted result of RMR were tested by paired t-test. Correlation of measured date was obtained by Pearson correlation coefficient. The value of predicted RMR and measured RMR were significantly different in these obese subjects. (p < 0.001). The difference between RMR cardiorespiratory fitness and cardiorespiratory fitness showed significant correlation (r=0.67, p < 0.05).

[Conclusion]

The current formulas of predicted RMR have limited the evaluation of measured RMR for Korean obese men. Therefore, this study suggests that new formula should be designed for Korean in order to obtain more accurate results in obese.