Body Size Phenotypes Research Articles

Prevalence of Metabolically Discordant Phenotypes in a Mediterranean Population—the Imap Study

To study the prevalence and correlates of body size phenotypes in an adult Spanish population. We undertook a cross-sectional analysis in a random sample of 2,270 individuals. We defined six body size phenotypes based on body mass index category (normal-weight, 18.5 to 24.9 kg/m2; overweight, 25 to 29.9 kg/m2; obese, ≥30.0 kg/m2) and the presence of ≤1 (metabolically healthy) or ≥2 (metabolically abnormal) cardiometabolic abnormalities: metabolically healthy normal-weight (MHNW), metabolically abnormal normal-weight (MANW), metabolically healthy overweight (MHOW), metabolically abnormal overweight (MAOW), metabolically healthy obese (MHO), and metabolically abnormal obese (MAO). We considered four cardiometabolic abnormalities: systolic and/or diastolic blood pressure ≥130/85 mm Hg, triglycerides ≥150 mg/dL, high-density-lipoprotein cholesterol levels <40/<50 mg/dL in men/women, and elevated glucose (fasting plasma glucose ≥100 mg/dL or previous diabetes). The prevalence of the MHO, MHOW, and MANW phenotypes was 2.2, 13.9, and 7.9%, respectively. Whereas 9.6% of obese and 32.6% of overweight individuals were metabolically healthy, 21.3% of the normal-weight subjects were metabolically abnormal. A multivariate regression model (adjusted for age, sex, and waist circumference) showed that age >40 years, male sex, and higher waist circumference were independently associated with the metabolically abnormal phenotype MANW, whereas younger age, female sex, and lower waist circumference were independently associated with the metabolically healthy phenotypes. The prevalence of MHO in our population is low and is more common in women and younger people. In contrast, a high proportion of normal-weight individuals (mainly over 40 years of age) in our population show cardiometabolic abnormalities.

A metabolically healthy obese phenotype in hispanic participants in the IRAS family study.

ObjectiveSome obese individuals appear to be protected from developing type 2 diabetes mellitus and cardiovascular disease (CVD). This has led to characterizing body size phenotypes based on cardiometabolic risk factors specifically as obese or overweight, and as metabolically healthy (MH) or metabolically abnormal (MA) based upon blood pressure, lipids, glucose homeostasis and inflammatory parameters. The aim of this study was to measure the prevalence of and describe fat distribution across these phenotypes in a minority population.Design and MethodsHispanic participants (N=1054) in the IRAS Family Study were categorized into different body size phenotypes. Computed tomography (CT) abdominal scans were evaluated for measures of non-alcoholic fatty liver disease (NAFLD) and abdominal fat distribution. Statistical models adjusting for familial relationships were estimated.ResultsSeventy percent (70%) of the Hispanic cohort was overweight (32%) or obese (38%). Forty-one percent (n=138) of overweight participants and 19% (n=74) of obese participants met criteria for MH. Adjusted analyses showed the MH phenotype was associated with lower visceral adipose tissue (VAT) and higher liver density (indicating lower fat content) in obese participants (p=0.0005 and p=0.0002, respectively), and lower VAT but not liver density in overweight participants (p=0.008 and p=0.162, respectively) compared to their MA counterparts. Odds of NAFLD were reduced in MH obese (OR=0.34, p=0.0007) compared to MA obese. VAT did not differ between MH obese or overweight and normal weight groups.ConclusionsThese findings suggest that lower levels of visceral and liver fat, despite overall increased total body fat, may be a defining feature of MH obesity in Hispanic Americans.

Liver enzymes and vitamin D levels in metabolically healthy but obese individuals: Korean National Health and Nutrition Examination Survey

ObjectiveIncreased liver enzymes and decreased vitamin D levels are associated with insulin resistance and type 2 diabetes. We examined liver enzymes and vitamin D levels in metabolically healthy but obese (MHO) individuals and compared the values with those of other body size phenotypes in the Korean population. Materials/MethodsA total of 16,190 people over the age of 18years were analyzed using data from the Fourth Korean National Health and Nutrition Examination Survey, which is a nationally representative survey. Body size phenotypes were classified into four groups by body mass index (BMI) and number of metabolic syndrome components. ResultsThe prevalence of MHO was 14.9% in the entire population and 47.7% in the obese population. In a correlation analysis adjusted for age, sex, and BMI, AST and ALT levels were positively correlated with insulin resistance and cardiometabolic risk factors of the metabolic syndrome, whereas vitamin D level was negatively correlated with these variables. MHO individuals had significantly lower concentrations of AST and ALT compared to metabolically abnormal obese (MAO) subjects, although vitamin D levels were not significantly different. Furthermore, a multiple logistic regression analysis revealed that MHO individuals had lower risk of liver enzyme abnormality compared to MAO after adjusting for potential confounding factors. However, the risk of vitamin D deficiency was not significantly different among groups with different body size phenotypes. ConclusionsAlthough both liver enzymes and vitamin D levels are related to insulin resistance and metabolic syndrome, only liver enzymes were independently associated with MHO phenotype.

Changes in the expression of four heat shock proteins during the aging process in Brachionus calyciflorus (rotifera)

Heat shock proteins (HSPs) are molecular chaperones and have an important role in the refolding and degradation of misfolded proteins, and these functions are related to aging. Rotifer is a useful model organism in aging research, owing to small body size (0.1-1mm), short lifespan (6-14days), and senescence phenotypes that can be measured relatively easily. Therefore, we used rotifer as a model to determine the role of four typical hsp genes on the aging process in order to provide a better understanding of rotifer aging. We cloned cDNA encoding hsp genes (hsp40, hsp60, hsp70, and hsp90) from the rotifer Brachionus calyciflorus Pallas, analyzed their molecular characteristics, determined its modulatory response under different temperatures and H2O2 concentrations and investigated the changes in expression of these genes during the aging process. We found that Bchsp70 mRNA expression significantly decreased with aging. In addition, we also studied the effects of dietary restriction (DR) and vitamin E on rotifer lifespan and reproduction and analyzed the changes in expression of these four Bchsp genes in rotifers treated with DR and vitamin E. The results showed that DR extended the lifespan of rotifers and reduced their fecundity, whereas vitamin E had no significant effect on rotifer lifespan or reproduction. Real-time PCR indicated that DR increased the expression of these four Bchsps. However, vitamin E only improved the expression of Bchsp60, and reduced the expression of Bchsp40, Bchsp70, and Bchsp90. DR pretreatment also increased rotifer survival rate under paraquat-induced oxidative stress. These results indicated that hsp genes had an important role in the anti-aging process.

Using RNA-mediated Interference Feeding Strategy to Screen for Genes Involved in Body Size Regulation in the Nematode &lt;em&gt;C. elegans&lt;/em&gt;

Double-strand RNA-mediated interference (RNAi) is an effective strategy to knock down target gene expression1-3. It has been applied to many model systems including plants, invertebrates and vertebrates. There are various methods to achieve RNAi in vivo4,5. For example, the target gene may be transformed into an RNAi vector, and then either permanently or transiently transformed into cell lines or primary cells to achieve gene knockdown effects; alternatively synthesized double-strand oligonucleotides from specific target genes (RNAi oligos) may be transiently transformed into cell lines or primary cells to silence target genes; or synthesized double-strand RNA molecules may be microinjected into an organism. Since the nematode C. elegans uses bacteria as a food source, feeding the animals with bacteria expressing double-strand RNA against target genes provides a viable strategy6. Here we present an RNAi feeding method to score body size phenotype. Body size in C. elegans is regulated primarily by the TGF- β - like ligand DBL-1, so this assay is appropriate for identification of TGF-β signaling components7. We used different strains including two RNAi hypersensitive strains to repeat the RNAi feeding experiments. Our results showed that rrf-3 strain gave us the best expected RNAi phenotype. The method is easy to perform, reproducible, and easily quantified. Furthermore, our protocol minimizes the use of specialized equipment, so it is suitable for smaller laboratories or those at predominantly undergraduate institutions.

Using RNA-mediated Interference Feeding Strategy to Screen for Genes Involved in Body Size Regulation in the Nematode &lt;em&gt;C. elegans&lt;/em&gt;

Double-strand RNA-mediated interference (RNAi) is an effective strategy to knock down target gene expression. It has been applied to many model systems including plants, invertebrates and vertebrates. There are various methods to achieve RNAi in vivo. For example, the target gene may be transformed into an RNAi vector, and then either permanently or transiently transformed into cell lines or primary cells to achieve gene knockdown effects; alternatively synthesized double-strand oligonucleotides from specific target genes (RNAi oligos) may be transiently transformed into cell lines or primary cells to silence target genes; or synthesized double-strand RNA molecules may be microinjected into an organism. Since the nematode C. elegans uses bacteria as a food source, feeding the animals with bacteria expressing double-strand RNA against target genes provides a viable strategy. Here we present an RNAi feeding method to score body size phenotype. Body size in C. elegans is regulated primarily by the TGF- β-llike ligand DBL-1, so this assay is appropriate for identification of TGF-β signaling components. We used different strains including two RNAi hypersensitive strains to repeat the RNAi feeding experiments. Our results showed that rrf-3 strain gave us the best expected RNAi phenotype. The method is easy to perform, reproducible, and easily quantified. Furthermore, our protocol minimizes the use of specialized equipment, so it is suitable for smaller laboratories or those at predominantly undergraduate institutions.

Body Size Phenotypes and Low Muscle Mass: The Korean Sarcopenic Obesity Study (KSOS)

Unique subsets of body size phenotypes seem to be more prone or more resistant to the development of obesity-associated metabolic disorders, although the underlying mechanism is not yet clearly understood. We investigated the prevalence and risk of low muscle mass in subjects who are classified as either metabolically healthy normal weight (MHNW), metabolically abnormal but normal weight (MANW), metabolically healthy obese (MHO), or metabolically abnormal obese (MAO). Subjects were classified based on body mass index and presence of metabolic syndrome. Thigh muscle cross-sectional area was evaluated using computed tomography as an index of muscle mass in 492 apparently healthy adults enrolled in the Korean Sarcopenic Obesity Study (KSOS), an ongoing prospective observational cohort study. Low muscle mass was defined as thigh muscle cross-sectional area divided by weight (percent) of <1 SD below the mean values of young adults in both sexes. The prevalence rates of low muscle mass in MHNW, MANW, MHO, and MAO subjects were 6.2%, 17.8%, 23.2%, and 33.7%, respectively. In a multiple logistic regression analysis, men with the MANW phenotype showed a remarkably increased risk of low muscle mass (odds ratio = 11.30, 95% confidence interval, 1.73-73.28) compared with those with MHNW. Furthermore, in both men and women, MHO or MAO subjects had higher odds ratios of low muscle mass compared with MHNW subjects. The present study suggests that low muscle mass may be associated with different metabolic consequences according to body size phenotype.

Convergent evolutionary processes driven by foraging opportunity in two sympatric morph pairs of Arctic charr with contrasting post-glacial origins

The expression of two or more discrete phenotypes amongst individuals within a species (morphs) provides multiple modes upon which selection can act semi-independently, and thus may be an important stage in speciation. In the present study, we compared two sympatric morph systems aiming to address hypotheses related to their evolutionary origin. Arctic charr in sympatry in Loch Tay, Scotland, exhibit one of two discrete, alternative body size phenotypes at maturity (large or small body size). Arctic charr in Loch Awe segregate into two temporally segregated spawning groups (breeding in either spring or autumn). Mitochondrial DNA restriction fragment length polymorphism analysis showed that the morph pairs in both lakes comprise separate gene pools, although segregation of the Loch Awe morphs is more subtle than that of Loch Tay. We conclude that the Loch Awe morphs diverged in situ (within the lake), whereas Loch Tay morphs most likely arose through multiple invasions by different ancestral groups that segregated before post-glacial invasion (i.e. in allopatry). Both morph pairs showed clear trophic segregation between planktonic and benthic resources (measured by stable isotope analysis) but this was significantly less distinct in Loch Tay than in Loch Awe. By contrast, both inter-morph morphological and life-history differences were more subtle in Loch Awe than in Loch Tay. The strong ecological but relatively weak morphological and life-history divergence of the in situ derived morphs compared to morphs with allopatric origins indicates a strong link between early ecological and subsequent genetic divergence of sympatric origin emerging species pairs. The emergence of parallel specialisms despite distinct genetic origins of these morph pairs suggests that the effect of available foraging opportunities may be at least as important as genetic origin in structuring sympatric divergence in post-glacial fishes with high levels of phenotypic plasticity. © 2012 The Linnean Society of London, Biological Journal of the Linnean Society, 2012, ••, ••–••.

Body size phenotypes are heritable and mediate fecundity but not fitness in the lepidopteran frugivore Cydia pomonella

The inheritance and functional roles of quantitative traits are central concerns of evolutionary ecology. We report two sets of experiments that investigated the heritability and reproductive consequences of body size phenotypes in a globally distributed lepidopteran frugivore, Cydia pomonella (L.). In our first set of experiments, we tested the hypotheses that (1) body size is heritable and (2) parental body size mediates egg production and offspring survival. Midparent-offspring regression analyses revealed that body mass is highly heritable for females and moderately heritable for males. The contribution of fathers to estimates of additive genetic variance was slightly greater than for mothers. Egg production increased with mean parental size, but offspring survival rates were equivalent. Based on this result, we tested two additional hypotheses in a second set of experiments: (3) male size moderates female egg production and egg fertility and (4) egg production, egg fertility, and offspring survival rate are influenced by female mating opportunities. Females paired with large males produced more eggs and a higher proportion of fertile eggs than females paired with small males. Females with multiple mating opportunities produced more fertile eggs than females paired with a single male. However, egg production and offspring survival rates were unaffected by the number of mating opportunities. Our experiments demonstrate that body mass is heritable in C. pomonella and that size phenotypes may mediate fecundity but not fitness. We conclude that male size can influence egg production and fertility, but female mate choice also plays a role in determining egg fertility.

Body Size Phenotypes and Inflammation in the Women's Health Initiative Observational Study

Individuals with "metabolically benign" obesity (obesity unaccompanied by hypertension, dyslipidemia, and diabetes) are not at elevated 10-year risk of cardiovascular disease (CVD) compared to normal weight individuals. It remains unclear whether these obese individuals or normal weight individuals with clustering of cardiometabolic factors display heightened immune activity. Therefore, we characterized levels of acute-phase reactants (C-reactive protein (CRP), interleukin-6 (IL-6), tumor necrosis factor-α (TNF-α), white blood cell (WBC) count), adhesion molecules (E-selectin, vascular cell adhesion molecule-1), and coagulation products (fibrinogen, plasminogen activator inhibitor-1 (PAI-1)) among four body size phenotypes (normal weight with 0/1 vs. ≥2 metabolic syndrome components/diabetes and overweight/obesity with 0/1 vs. ≥2 metabolic syndrome components/diabetes) in cross-sectional analyses of 1,889 postmenopausal women from the Women's Health Initiative Observational Study (WHI-OS) nested case-control stroke study. Higher levels of all three inflammatory marker categories were found among women with overweight/obesity or ≥2 metabolic syndrome components or diabetes. Compared to normal weight women with 0 or 1 metabolic syndrome components, normal weight women with ≥2 metabolic syndrome components or diabetes were more likely to have ≥3 inflammatory markers in the top quartile (multivariate odds ratio (OR) 2.0, 95% confidence interval (CI): 1.3-3.0), as were overweight/obese women with 0 or 1 metabolic syndrome components (OR 2.3; 95% CI: 1.5-3.5). Overweight/obese women with ≥2 metabolic syndrome components or diabetes had the highest OR (OR 4.2; 95% CI: 2.9-5.9). Despite findings that metabolically benign obese individuals are not at increased 10-year risk of CVD compared to normal weight individuals, the current results suggest that overweight/obese women without clustering of cardiometabolic risk factors still possess abnormal levels of inflammatory markers.

The parallel evolution of dwarfism in Arctic charr is accompanied by adaptive divergence in mTOR-pathway gene expression

Ecological factors have a major role in shaping natural variation in body size, although the underlying mechanisms are poorly understood. Icelandic Arctic charr (Salvelinus alpinus L.) populations represent an ideal model to understand body-size evolution, because adult dwarfism has arisen independently on multiple occasions in response to parallel environmental pressures. The mechanistic target of rapamycin (mTOR) pathway transmits signals from the environment to control cellular growth and is a primary candidate to be under selection for the dwarf phenotype. To test this hypothesis, we modified 'inputs' to this pathway in five dwarf and two generalist populations (with ancestral life history and body-size traits), using a standardized manipulation of food intake in a common environment. The skeletal muscle transcript levels of 21 mTOR-pathway genes were quantified in 274 individuals (∼6000 datapoints), and statistical modelling was used to elucidate sources of variation. Constitutive expression differences between populations were the main component of variation for around three-quarters of the studied genes, irrespective of nutritional-state and body-size phenotype. There was evidence for stabilizing selection acting among populations, conserving the nutritionally dependent regulation of pathway genes controlling muscle atrophy. There were three genes (mTOR, 4E-BP-1 and IGFBP4), where the expression variation between dwarf and generalist populations exceeded the between-population variation. Divergence in the expression of these candidate adaptive genes was most evident during a period of rapid growth following sustained fasting and was directionally consistent with their functions regulating growth and protein synthesis. We concluded that selection has operated efficiently to shape gene expression evolution in Icelandic charr populations and that the regulation of certain mTOR-pathway genes evolved adaptively in locations favouring dwarfism, resulting in reduced muscle protein accretion under growth-favouring conditions.

DFOXO‐independent effects of reduced insulin‐like signaling in Drosophila

The insulin/insulin-like growth factor-like signaling (IIS) pathway in metazoans has evolutionarily conserved roles in growth control, metabolic homeostasis, stress responses, reproduction, and lifespan. Genetic manipulations that reduce IIS in the nematode worm Caenorhabditis elegans, the fruit fly Drosophila melanogaster, and the mouse have been shown not only to produce substantial increases in lifespan but also to ameliorate several age-related diseases. In C. elegans, the multitude of phenotypes produced by the reduction in IIS are all suppressed in the absence of the worm FOXO transcription factor, DAF-16, suggesting that they are all under common regulation. It is not yet clear in other animal models whether the activity of FOXOs mediate all of the physiological effects of reduced IIS, especially increased lifespan. We have addressed this issue by examining the effects of reduced IIS in the absence of dFOXO in Drosophila, using a newly generated null allele of dfoxo. We found that the removal of dFOXO almost completely blocks IIS-dependent lifespan extension. However, unlike in C. elegans, removal of dFOXO does not suppress the body size, fecundity, or oxidative stress resistance phenotypes of IIS-compromised flies. In contrast, IIS-dependent xenobiotic resistance is fully dependent on dFOXO activity. Our results therefore suggest that there is evolutionary divergence in the downstream mechanisms that mediate the effects of IIS. They also imply that in Drosophila, additional factors act alongside dFOXO to produce IIS-dependent responses in body size, fecundity, and oxidative stress resistance and that these phenotypes are not causal in IIS-mediated extension of lifespan.

Maternal High-Fat Diet Effects on Third-Generation Female Body Size via the Paternal Lineage

The health consequences of in utero exposure to maternal obesity on future generations are concerning because they contribute to increased rates of diabetes, cardiovascular disease, and metabolic syndrome. We previously reported that maternal high-fat diet exposure in mice resulted in an increase in body size and reduced insulin sensitivity that persisted across two generations via both maternal and paternal lineages. However, because the first generation's primordial germ cells may be affected by gestational exposure, analysis of phenotype transmission into a third generation (F3) is necessary to determine whether stable epigenetic programming has occurred. Therefore, we have examined the body size and insulin sensitivity of male and female F3 offspring. We found that only females displayed the increased body size phenotype, and this effect was only passed on via the paternal lineage. The finding of a paternally transmitted phenotype to F3 female offspring supports a stable germline-based transgenerational mode of inheritance; thus we hypothesized that imprinted genes may be involved in this epigenetic programming. Using a quantitative TaqMan Array for imprinted genes to examine paternally or maternally expressed loci in F3 female livers, we detected a potential dynamic pattern of paternally expressed genes from the paternal lineage that was not noted in the maternal lineage. These findings suggest that the environmental influence on developmental regulation of growth and body size may be the result of broad programming events at imprinted loci, thereby providing sex specificity to both the transmission and inheritance of traits related to disease predisposition.

Quantitative genetics of human morphology and obesity-related phenotypes in nuclear families from the Greater Bilbao (Spain): Comparison with other populations

Background: It is well established that variation of soft-tissue traits is less influenced by the genetic component than skeletal traits. However, it is still unclear whether heritabilities (h2) of obesity-related phenotypes present a common pattern across populations.Aim: To estimate familial resemblance and heritability of body size, shape and composition phenotypes and to compare these results with those from other populations.Subjects and methods: The subject group consisted of 533 nuclear families living in Greater Bilbao and included 1702 individuals aged 2–61 years. Familial correlations and h2 were estimated for 29 anthropometric phenotypes (19 simple measures, three derived factors, four obesity indices and the three Heath-Carter somatotype components) using MAN and SOLAR programmes.Results: All phenotypes were influenced by additive genetic factors with narrow sense heritabilities ranging from 0.28–0.69. In general, skeletal traits exhibited the highest h2, whereas phenotypes defining the amount of adipose tissue, particularly central fat, were less determined by genetic factors.Conclusions: Familial correlations and heritability estimates of body morphology and composition from the Greater Bilbao sample were within the range observed in other studies. The lower heritability detected for central fat has also been found in some other populations, but further investigations in different populations using the same anthropometric traits and estimation methods are needed in order to obtain more robust conclusions.

Linkage mapping of principal components for femoral biomechanical performance in a reciprocal HCB-8 × HCB-23 intercross

Studies of bone genetics have addressed an array of related phenotypes, including various measures of biomechanical performance, bone size, bone, shape, and bone mineral density. These phenotypes are not independent, resulting in redundancy of the information they provide. Principal component (PC) analysis transforms multiple phenotype data to a new set of orthogonal “synthetic” phenotypes. We performed PC analysis on 17 femoral biomechanical, anatomic, and body size phenotypes in a reciprocal intercross of HcB-8 and HcB-23, accounting for 80% of the variance in 4 PCs. Three of the 4 PCs were mapped in the cross. The linkage analysis revealed a quantitative trait locus (QTL) with LOD = 4.7 for PC2 at 16 cM on chromosome 19 that was not detected using the directly measured phenotypes. The chromosome 19 QTL falls within a ~ 10 megabase interval, with Osf1 as a positional candidate gene. PC QTLs were also found on chromosomes 1, 2, 4, 6, and 10 that coincided with those identified for directly measured or calculated material property phenotypes. The novel chromosome 19 QTL illustrates the power advantage that attends use of PC phenotypes for linkage mapping. Constraint of the chromosome 19 candidate interval illustrates an important advantage of experimental crosses between recombinant congenic mouse strains.

Evidence-based politics: How successful have government reviews been as policy instruments to reduce health inequalities in England?

Increased cardiovascular disease and mortality risk in metabolically healthy obese (MHO) individuals remain highly controversial. Several studies suggested risk while others do not. The traditional cardiovascular risk factors may be insufficient to demonstrate the complete range of metabolic abnormalities in MHO individuals. Hence, we aimed to compare the prevalence of elevated lipoprotein (a), apolipoprotein B, and uric acid (UA) levels, apolipoprotein B/apolipoprotein A1 ratio, and visceral adiposity index (VAI) scores, and low apolipoprotein A1 levels among 6 body size phenotypes (normal weight with and without metabolic abnormalities, overweight with and without metabolic abnormalities, and obese with or without metabolic abnormalities).We conducted a cross-sectional analysis of 7765 Chinese adults using data from the nationwide China Health and Nutrition Survey 2009. MHO persons had intermediate prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low apolipoprotein A1 levels between metabolically healthy normal-weight (MHNW) and metabolically abnormal obese individuals (P < 0.001 for all comparisons). Elevated apolipoprotein B and UA concentrations, apolipoprotein B/apolipoprotein A1 ratio, and VAI scores were all strongly associated with the MHO phenotype (all P < 0.01).Prevalence of elevated apolipoprotein B and UA levels, apolipoprotein B/apolipoprotein A1 ratio and VAI scores, and low levels of apolipoprotein A1 was higher among MHO persons than among MHNW individuals. The elevated levels of the nontraditional risk factors and VAI scores in MHO persons could contribute to the increased cardiovascular disease risk observed in long-term studies.

The Obese Without Cardiometabolic Risk Factor Clustering and the Normal Weight With Cardiometabolic Risk Factor Clustering Prevalence and Correlates of 2 Phenotypes Among the US Population (NHANES 1999–2004)

The individual risk of cardiovascular disease (CVD) may depend on both body size and the metabolic profile. Individuals with a similar body mass index (BMI) may express a different clustering of cardiometabolic risk factors (variable body size phenotypes). There are few data regarding the prevalence and correlates of two body size phenotypes, one, a subset of normal-weight individuals displaying cardiometabolic risk factor clustering, and the other a subset of obese individuals resistant to the development of the adiposity-associated cardiometabolic abnormalities. These parameters were examined in an observational study involving 5440 participants of the National Health and Nutrition Examination Surveys (NHANES) 1999-2004 database who were 20 years of age and older. Individuals were classified according to their BMI as either normal weight, <25.0; overweight, 25.0-29.9; and obese, ≥30.0 [calculated as weight in kilograms divided by height in meters squared]. The cardiometabolic abnormalities include elevated blood pressure and insulin resistance; elevated levels of triglycerides, fasting glucose, and C-reactive protein; and reduced level of high density lipoprotein cholesterol (HDL-C). The metabolically healthy phenotype is defined as ≤2 metabolic abnormalities and the metabolically abnormal as ≥3 metabolic abnormalities. Each of 6 body size phenotypes were evaluated: normal-weight, overweight, and obese individuals with or without cardiometabolic abnormalities. A multivariate adjustment regression model was used to calculate the independent risk factors for CVD. The data show that, of the phenotypes expressed as percentage of each BMI group, 51.3% (approximately 35.9 million adults) of overweight adults and 31.7% (approximately 19.5 million adults) of obese adults were metabolically healthy, whereas 23.5% (approximately 16.3 million adults) of normal-weight adults were metabolically abnormal. Among normal-weight individuals, risk factors independently associated with the metabolically abnormal phenotype were older age, larger waist circumference, and lower physical activity. Among overweight and obese individuals, independent risk factors for expression of the metabolically healthy phenotype were younger age, smaller waist circumference, higher physical activity, and non-Hispanic black race/ethnicity. These findings indicate that among US adults there is a high prevalence of overweight and obese individuals who are metabolically healthy, and a high prevalence of normal-weight individuals who express a clustering of cardiometabolic abnormalities.

Autosomal variation for male body size and sperm competition phenotypes is uncorrelated in Drosophila melanogaster

Correlations between male body size and phenotypes impacting post-copulatory sexual selection are commonly observed during the manipulation of male body size by environmental rearing conditions. Here, we control for environmental influences and test for genetic correlations between natural variation in male body size and phenotypes affecting post-copulatory sexual selection in Drosophila melanogaster. Dry weights of virgin males from 90 second-chromosome and 88 third-chromosome substitution lines were measured. Highly significant line effects (p<0.001) documented a genetic basis to variation in male body size. No significant correlations were identified between male body size and the components of sperm competitive ability. These results suggest that natural autosomal variation for male body size has little impact on post-copulatory sexual selection. If genetic correlations exist between male body size and post-copulatory sexual selection then variation in the sex chromosomes are likely candidates, as might be expected if sexually antagonistic coevolution was responsible.

Regulation of Caenorhabditis elegans body size and male tail development by the novel gene lon-8.

BackgroundIn C. elegans and other nematode species, body size is determined by the composition of the extracellular cuticle as well as by the nuclear DNA content of the underlying hypodermis. Mutants that are defective in these processes can exhibit either a short or a long body size phenotype. Several mutations that give a long body size (Lon) phenotype have been characterized and found to be regulated by the DBL-1/TGF-β pathway, that controls post-embryonic growth and male tail development.ResultsHere we characterize a novel gene affecting body size. lon-8 encodes a secreted product of the hypodermis that is highly conserved in Rhabditid nematodes. lon-8 regulates larval elongation as well as male tail development. In both processes, lon-8 appears to function independently of the Sma/Mab pathway. Rather, lon-8 genetically interacts with dpy-11 and dpy-18, which encode cuticle collagen modifying enzymes.ConclusionThe novel gene lon-8 encodes a secreted product of the hypodermis that controls body size and male ray morphology in C. elegans. lon-8 genetically interacts with enzymes that affect the composition of the cuticle.

Transcriptional repressor and activator activities of SMA-9 contribute differentially to BMP-related signaling outputs

In the nematode Caenorhabditis elegans, the BMP-related growth factor DBL-1 regulates body size and male tail morphogenesis via a conserved receptor/Smad signaling pathway. Smads are transcription factors, but rely on transcription cofactors for appropriate regulation of target genes in response to TGF-β- and BMP-related signals. In the DBL-1 pathway, sma-9 encodes multiple zinc finger transcription factors homologous to Drosophila Schnurri, which functions in Dpp/BMP signaling. We have studied the molecular functions of SMA-9 as a model for transcription cofactor-dependent regulation of gene expression. Using SMA-9 fusions to known transcriptional activators and repressors, we demonstrate that SMA-9 acts primarily as a transcriptional repressor in body size regulation in vivo. In contrast, both activator and repressor functions contribute to male tail patterning . We further show that different SMA-9 regions have intrinsic repressor and activator activities using a yeast transcription assay. We use microarray analysis to identify transcriptional target genes in body size regulation. Consistent with the importance of repression in mediating body size regulation, we find more repressed genes than activated genes in this pool. Finally, we identify five transcriptional targets with body size and/or male tail patterning phenotypes, including transcription factors related to Runx and fos and signaling molecules related to hedgehog and patched. Our results thus suggest that SMA-9 products function differentially as transcriptional repressors and activators in DBL-1/BMP pathway regulated body size and male tail morphogenesis.