Fat Body Size Research Articles

Fear-of-intimacy-mediated zinc transport is required for Drosophila fat body endoreplication

BackgroundEndoreplication is involved in the development and function of many organs, the pathologic process of several diseases. However, the metabolic underpinnings and regulation of endoreplication have yet to be well clarified.ResultsHere, we showed that a zinc transporter fear-of-intimacy (foi) is necessary for Drosophila fat body endoreplication. foi knockdown in the fat body led to fat body cell nuclei failure to attain standard size, decreased fat body size and pupal lethality. These phenotypes could be modulated by either altered expression of genes involved in zinc metabolism or intervention of dietary zinc levels. Further studies indicated that the intracellular depletion of zinc caused by foi knockdown results in oxidative stress, which activates the ROS-JNK signaling pathway, and then inhibits the expression of Myc, which is required for tissue endoreplication and larval growth in Drosophila.ConclusionsOur results indicated that FOI is critical in coordinating fat body endoreplication and larval growth in Drosophila. Our study provides a novel insight into the relationship between zinc and endoreplication in insects and may provide a reference for relevant mammalian studies.

DNA G-quadruplex structure participates in regulation of lipid metabolism through acyl-CoA binding protein.

G-quadruplex structure (G4) is a type of DNA secondary structure that widely exists in the genomes of many organisms. G4s are believed to participate in multiple biological processes. Acyl-CoA binding protein (ACBP), a ubiquitously expressed and highly conserved protein in eukaryotic cells, plays important roles in lipid metabolism by transporting and protecting acyl-CoA esters. Here, we report the functional identification of a G4 in the promoter of the ACBP gene in silkworm and human cancer cells. We found that G4 exists as a conserved element in the promoters of ACBP genes in invertebrates and vertebrates. The BmACBP G4 bound with G4-binding protein LARK regulated BmACBP transcription, which was blocked by the G4 stabilizer pyridostatin (PDS) and G4 antisense oligonucleotides. PDS treatment with fifth instar silkworm larvae decreased the BmACBP expression and triacylglycerides (TAG) level, resulting in reductions in fat body mass, body size and weight and growth and metamorphic rates. PDS treatment and knocking out of the HsACBP G4 in human hepatic adenocarcinoma HepG2 cells inhibited the expression of HsACBP and decreased the TAG level and cell proliferation. Altogether, our findings suggest that G4 of the ACBP genes is involved in regulation of lipid metabolism processes in invertebrates and vertebrates.

Association of variants in FABP4, FASN, SCD, SREBP1 and TCAP genes with intramuscular fat, carcass traits and body size in Chinese Qinchuan cattle

This study aimed to genotype the variants in FABP4, FASN, SCD, SREBP1 and TCAP genes, and to analyze their associations with intramuscular fat (IMF) content, carcass traits and body size in Chinese Qinchuan cattle (QC). The association studies showed that the FABP4 c.220A > G polymorphism was significantly associated with ultrasound longissimus muscle depth (ULMD) and IMF, the FASN g.16024A > G polymorphism was significantly associated with ULMD and some body size traits, the SREBP1 84 bp indel was significantly associated with back fat thickness, ULMD and some body size traits. The frequencies of well-characterized A allele in FABP4 c.220A > G in Korean cattle (KOR) and Japanese Black cattle (JB), T allele in SCD g.8586C > T in KOR, SS genotype in SREBP1 84 bp indel in KOR and JB, DELDEL genotype in TCAP g.592-597CTGCAGinsdel in KOR were significantly higher than in Chinese cattle breeds. Thus, the associated four polymorphisms were expected to be genetic selection markers for meat quality, carcass traits and body size of QC.

Monitoring bee health in European agro-ecosystems using wing morphology and fat bodies

Current global change substantially threatens pollinators, which directly impacts the pollination services underpinning the stability, structure and functioning of ecosystems. Amongst these threats, many synergistic drivers, such as habitat destruction and fragmentation, increasing use of agrochemicals, decreasing resource diversity, as well as climate change, are known to affect wild and managed bees. Therefore, reliable indicators for pollinator sensitivity to such threats are needed. Biological traits, such as phenotype (e.g. shape, size and asymmetry) and storage reserves (e.g. fat body size), are important pollinator traits linked to reproductive success, immunity, resilience and foraging efficiency and, therefore, could serve as valuable markers of bee health and pollination service potential. This data paper contains an extensive dataset of wing morphology and fat body content for the European honeybee (Apis mellifera) and the buff-tailed bumblebee (Bombus terrestris) sampled at 128 sites across eight European countries in landscape gradients dominated by two major bee-pollinated crops (apple and oilseed rape), before and after focal crop bloom and potential pesticide exposure. The dataset also includes environmental metrics of each sampling site, namely landscape structure and pesticide use. The data offer the opportunity to test whether variation in the phenotype and fat bodies of bees is structured by environmental factors and drivers of global change. Overall, the dataset provides valuable information to identify which environmental threats predominantly contribute to the modification of these traits.

Genome-wide association studies revealed candidate genes for tail fat deposition and body size in the Hulun Buir sheep.

Fat-tailed sheep have a unique characteristic of depositing fat in their tails. In the present study, we conducted genome-wide association studies (GWAS) on traits related to tail fat deposition and body size in the Hulun Buir sheep. A total number of 300 individuals belonging to two fat-tailed lines of the Hulun Buir sheep breed genotyped with the Ovine Infinium HD SNP BeadChip were included in the current study. Two mixed models, one for continuous and one for binary phenotypic traits, were employed to analyse ten traits, that is, body length (BL), body height (BH), chest girth (CG), tail length (TL), tail width (TW), tail circumference (TC), carcass weight (CW), tail fat weight (TF), ratio of CW to TF (RCT) and tail type (TT). We identified 7, 6, 7, 2, 10 and 1 SNPs significantly associated with traits TF, CW, RCT, TW, TT and CG, respectively. Their associated genomic regions harboured 42 positional candidate genes. Out of them, 13 candidate genes including SMURF2, FBF1, DTNBP1, SETD7 and RBM11 have been associated with fat metabolism in sheep. The RBM11 gene has already been identified in a previous study on signatures of selection in this specific sheep population. Two more genes, that is, SMARCA5 and GAB1 were associated with body size in sheep. The present study has identified candidate genes that might be implicated in tail fat deposition and body size in sheep.

Different effects of accelerated development and enhanced growth on oxidative stress and telomere shortening in amphibian larvae

Organisms react to environmental changes through plastic responses that often involve physiological alterations with the potential to modify life-history traits and fitness. Environmentally induced shifts in growth and development in species with complex life cycles determine the timing of transitions between subsequent life stages, as well as body condition at transformation, which greatly determine survival at later stages. Here we show that spadefoot toad larvae surviving pond drying and predators experienced marked alterations in growth and development, and in their fat reserves, oxidative stress, and relative telomere length. Tadpoles accelerated development but reduced growth and consumed more fat reserves when facing pond drying. However, oxidative stress was buffered by increased antioxidant enzyme activity, and telomeres remained unchanged. Predators caused opposite effects: they reduced larval density, hence relaxing competition and allowing faster development and enhanced growth of survivors. Tadpoles surviving predators metamorphosed bigger and had larger fat bodies, increasing their short-term survival odds, but showed signs of oxidative stress and had shorter telomeres. Developmental acceleration and enhanced growth thus seemed to have different physiological consequences: reduced fat bodies and body size compromise short-term survival, but are reversible in the long run, whereas telomere shortening is non-reversible and could reduce long-term survival.

Effects of overwintering temperature on the survival of the black garden ant (Lasius niger)

The overwintering temperatures of ants might well be elevated due to climate change. We studied whether the overwintering temperature affects the survival of the queens and whole colonies of the black garden ant, Lasius niger (Linnaeus, 1758). In two consecutive years (2009, 2010) we collected mated, colony founding queens (n=280) from the urban area of Turku, Finland. Half of the queens overwintered in +7 to +8°C and the other half in +2°C. After the overwintering period, we determined their survival rate and measured the body fat content, body size and immune defence (encapsulation rate) of overwintering queens. Using the same setup, we studied the survival of 1-year-old L. niger colonies (queen & workers). Overwintering at a lower temperature (+2°C) decreased the survival of workers. The survival of colony founding queens differed between years, but unlike with workers, the overwintering temperature did not affect their survival: neither in the colony experiment nor in the single queen experiment. All of the surviving queens managed to produce their worker offspring at the same rate. The relative amount of body fat of queens was higher for those who overwintered at a lower temperature, which is likely a result of lower energy consumption. We did not detect differences in the encapsulation rate between the temperature treatment groups. The ability of colony founding queens to tolerate wide overwintering temperature variations present in urban environments may explain the success of the colony in urban areas. As the colony grows, the overwintering chambers may extend more deeply into the ground. Thus, workers may not have to cope with such cold conditions as colony founding queens.

Association of early childhood abdominal circumference and weight gain with blood pressure at 36 months of age: secondary analysis of data from a prospective cohort study

ObjectivesTo assess whether changes in measures of fat distribution and body size during early life are associated with blood pressure at 36 months of age.DesignAnalysis of data collected from a...

Body composition and arsenic metabolism: a cross-sectional analysis in the Strong Heart Study.

ObjectiveThe objective of this study was to evaluate the association between measures of body composition and patterns of urine arsenic metabolites in the 1989–1991 baseline visit of the Strong Heart Study, a cardiovascular disease cohort of adults recruited from rural communities in Arizona, Oklahoma, North Dakota and South Dakota.MethodsWe evaluated 3,663 Strong Heart Study participants with urine arsenic species above the limit of detection and no missing data on body mass index, % body fat and fat free mass measured by bioelectrical impedance, waist circumference and other variables. We summarized urine arsenic species patterns as the relative contribution of inorganic (iAs), methylarsonate (MMA) and dimethylarsinate (DMA) species to their sum. We modeled the associations of % arsenic species biomarkers with body mass index, % body fat, fat free mass, and waist circumference categories in unadjusted regression models and in models including all measures of body composition. We also considered adjustment for arsenic exposure and demographics.ResultsIncreasing body mass index was associated with higher mean % DMA and lower mean % MMA before and after adjustment for sociodemographic variables, arsenic exposure, and for other measures of body composition. In unadjusted linear regression models, % DMA was 2.4 (2.1, 2.6) % higher per increase in body mass index category (< 25, ≥25 & <30, ≥30 & <35, ≥35 kg/m2), and % MMA was 1.6 (1.4, 1.7) % lower. Similar patterns were observed for % body fat, fat free mass, and waist circumference measures in unadjusted models and in models adjusted for potential confounders, but the associations were largely attenuated or disappeared when adjusted for body mass index.ConclusionMeasures of body size, especially body mass index, are associated with arsenic metabolism biomarkers. The association may be related to adiposity, fat free mass or body size. Future epidemiologic studies of arsenic should consider body mass index as a potential modifier for arsenic-related health effects.

Latitudinal patterns in phenotypic plasticity: the case of seasonal flexibility in lizards’ fat body size

Several studies published over the last years suggest that the ability of many species to cope with global change will be closely related to the current amount of plasticity for fitness-related traits. Thus, disentangling general patterns in phenotypic flexibility, which could be then included in models aimed to predict changes in species distribution, represent a central goal in the current ecological agenda. The climatic variability hypothesis (CVH) could be considered a timely and promising hypothesis since it provides an explicit link between climatic and geographic variables and phenotypic plasticity. Specifically, the CVH states that as the range of climatic fluctuation experienced by terrestrial animals increases with latitude, individuals at higher latitudes should present greater levels of phenotypic flexibility. Within this framework, here we evaluate the existence of latitudinal patterns in fat body size flexibility--estimated as the difference between maximum and minimum fat body size values observed throughout a year--for 59 lizard species, comprising the first evaluation of the CVH for a trait, other than thermic or metabolic characters, in ectothermic species. Conventional and phylogenetic analyses indicated a positive relationship between fat body size flexibility and latitude, and also between flexibility and temperature variability indexes. Together with previous findings our results suggest that: (1) latitudinal pattern for fitness-related traits, other than thermal characters, are beginning to emerge; (2) latitude is usually a better predictor of phenotypic plasticity than putative climatic variables; (3) hemispheric differences in climatic variability appears to be correlated with hemispheric differences in phenotypic plasticity.

A novel c.‐274C&gt;G polymorphism in bovine SIRT1 gene contributes to diminished promoter activity and is associated with increased body size

SIRT1, a mammalian homologue for yeast silent information regulator 2 (SIR2), is a NAD(+) -dependent deacetylase that belongs to the class III histone deacetylases. It plays an important role in diverse cellular processes, including stress resistance, mitochondrial function, suppression of inflammation and DNA repair. In this study, we screened and identified a novel polymorphism (c.-274C>G) in the SIRT1 promoter region. In silico prediction reveals that this SNP is in the core of cell cycle-dependent element (CDE)-binding motif. Interestingly, the G allele abolished a CDE-binding site, which suggested its functional significance. In the luciferase assay system, we found that the G allele-containing construct displayed a strikingly lower promoter activity compared with the C allele, which may downregulate SIRT1 expression levels. Additionally, we observed a significant association between the c.-274C>G polymorphism and growth traits in Nanyang cattle, suggesting that anomalous transcription factor-based repression of SIRT1 may increase bovine fat mass and body size.

Size and sex matter: infection dynamics of an invading parasite (the pentastome Raillietiella frenatus) in an invading host (the cane toad Rhinella marina)

Correlations between host phenotype and vulnerability to parasites can clarify the processes that enhance rates of parasitism, and the effects of parasites on their hosts. We studied an invasive parasite (the pentastome Raillietiella frenatus, subclass Pentastomida, order Cephalobaenida) infecting a new host (the invasive cane toad Rhinella marina), in tropical Australia. We dissected toads over a 27-month period to investigate seasonal changes in pentastome population dynamics and establish which aspects of host phenotype are related to infection. Pentastome prevalence and intensity varied seasonally; male toads were 4 times more likely to be infected than were females; and prevalence was highest in hosts of intermediate body size. The strong sex effect may reflect habitat or dietary divergence between the sexes, resulting in males encountering parasites more often. The relationship between pentastome prevalence and host size likely reflects a role for acquired immunity in preventing re-infection. Infection did not influence host body condition (fatbody size), suggesting that R. frenatus does not impose high energy costs in cane toads. Infected toads had heavier spleens (likely an immune response to infection) and larger testes (perhaps since reproductively active hosts have altered microhabitat use and/or immunocompetence) than did uninfected conspecifics. Although experimental studies are required to identify the causal bases of such patterns, our data confirm that infection status within a population can be strongly linked to host phenotypic traits.

P2-314 Relative body fat and blood pressure in children: a population based individually matched study in China

IntroductionNormative blood pressure (BP) percentiles in children recommended by the current guidelines vary with body size. Separating the effect of fat mass from that of total body size on BP...

Atrazine exposure affects growth, body condition and liver health in Xenopus laevis tadpoles

Six studies were performed regarding the effects of atrazine, the most frequently detected pesticide in fresh water in the US, on developing Xenopus laevis tadpoles exposed 5 days post-hatch through Nieuwkoop Faber Stage 62. The levels of atrazine tested included those potentially found in puddles, vernal ponds and runoff soon after application (200 and 400 μg/L) and a low level studied by a number of other investigators (25 μg/L). One study tested 0, 25 and 200 μg/L, another tested 0, 200 and 400 μg/L, while the remaining four studies tested 0 and 400 μg/L. During all exposures, mortality, growth, metamorphosis, sex ratio, fat body (a lipid storage organ) size and liver weights, both relative to body weight, were evaluated. In selected studies, feeding behavior was recorded, livers and fat bodies were histologically evaluated, liver glycogen and lipid content were determined by image analysis, and immunohistochemical detection of activated caspase-3 in hepatocytes was performed. The NOEC was 25 μg/L. None of these exposure levels changed sex ratios nor were intersex gonads noted, however, no definitive histological evaluation of the gonads was performed. Although a marginal increase in mortality at the 200 μg/L level was noted, this was not statistically significant. Nor was there an increase in mortality at 400 μg/L versus controls. At the 400 μg/L level, tadpoles were smaller than controls by 72 h of exposure and remained smaller throughout the entire exposure. Appetite was not decreased at any exposure level. Slowed metamorphosis was noted only at 400 μg/L in two of five studies. Livers were significantly smaller in the study that tested both 200 and 400 μg/L, yet no pathological changes or differences in glycogen or lipid stores were noted. However, livers from 400 μg/L exposed tadpoles had higher numbers of activated caspase-3 immunopositive cells suggesting increased rates of apoptosis. Fat body size decreased significantly after exposure to 200 and 400 μg/L although these organs still contained some lipid and lacked any pathology. Since this was noted across all studies, it was considered the most sensitive indicator of atrazine exposure measured. The changes noted in body and organ size at 200 and 400 μg/L atrazine indicated exposure throughout development compromised the tadpoles. Significant reductions in fat body size could potentially decrease their ability to survive the stresses of metamorphosis or reduce reproductive fitness as frogs rely on stored lipids for these processes.

Chronic exposure to high levels of atrazine alters expression of genes that regulate immune and growth-related functions in developing Xenopus laevis tadpoles

Atrazine is the most commonly detected pesticide in ground and surface waters, with seasonal spikes that often exceed the Environmental Protection Agency's “Recommended Water Quality Criterion” of 350 parts per billion (ppb). Although numerous studies have shown atrazine produces adverse effects on growth, development, immune and endocrine system functions in a wide range of species, few describe gene expression changes concurrent with atrazine-induced changes in phenotype during development. In this report, developing Xenopus laevis tadpoles were chronically exposed to 400ppb atrazine, an environmentally relevant concentration. Affymetrix microarrays and Taqman qRT-PCR were used to define gene expression changes that underlie atrazine-induced phenotypic alterations. Atrazine significantly reduced survival and growth (weight, length and fat body size) in male and female tadpoles. Microarray analysis showed atrazine altered expression of 44 genes in male tadpoles (18 upregulated, 26 downregulated) and 77 genes in female tadpoles (23 upregulated, 54 downregulated). Classification of the genes into functional groups showed the majority of genes were associated with the following biological functions: growth and metabolism, proteolysis, fibrinogen complex formation and immune regulation. Seven genes associated with immune system function, specifically defense molecules present in the skin (e.g. magainin II, levitide A, preprocarulein, skin granule protein), were significantly downregulated in female tadpoles. These results support the idea that environmental contaminants such as atrazine compromise important gene pathways during frog development that may, ultimately, be relevant to global amphibian decline.

Rictor/TORC2 Regulates Caenorhabditis elegans Fat Storage, Body Size, and Development through sgk-1

The target of rapamycin (TOR) kinase coordinately regulates fundamental metabolic and cellular processes to support growth, proliferation, survival, and differentiation, and consequently it has been proposed as a therapeutic target for the treatment of cancer, metabolic disease, and aging. The TOR kinase is found in two biochemically and functionally distinct complexes, termed TORC1 and TORC2. Aided by the compound rapamycin, which specifically inhibits TORC1, the role of TORC1 in regulating translation and cellular growth has been extensively studied. The physiological roles of TORC2 have remained largely elusive due to the lack of pharmacological inhibitors and its genetic lethality in mammals. Among potential targets of TORC2, the pro-survival kinase AKT has garnered much attention. Within the context of intact animals, however, the physiological consequences of phosphorylation of AKT by TORC2 remain poorly understood. Here we describe viable loss-of-function mutants in the Caenorhabditis elegans homolog of the TORC2-specific component, Rictor (CeRictor). These mutants display a mild developmental delay and decreased body size, but have increased lipid storage. These functions of CeRictor are not mediated through the regulation of AKT kinases or their major downstream target, the insulin-regulated FOXO transcription factor DAF-16. We found that loss of sgk-1, a homolog of the serum- and glucocorticoid-induced kinase, mimics the developmental, growth, and metabolic phenotypes of CeRictor mutants, while a novel, gain-of-function mutation in sgk-1 suppresses these phenotypes, indicating that SGK-1 is a mediator of CeRictor activity. These findings identify new physiological roles for TORC2, mediated by SGK, in regulation of C. elegans lipid accumulation and growth, and they challenge the notion that AKT is the primary effector of TORC2 function.

Three Boll Weevil Diapause Myths in Perspective

The boll weevil, Anthonomus grandis grandis Boheman (Coleoptera: Curculionidae), a serious pest of cotton, Gossypium hirsutum L, originated in Mesoamerica, but its contemporary distribution extends from the United States Cotton Belt to Argentina. Myths, dogma, and misperceptions that persist about the insect's diapause hinder the development of control strategies suitable to subtropical and tropical areas. Three salient myths are that diapause induction is governed by diet; diapause is universal; and diapause is accurately characterized by fat body size or lack of egg production. An examination of assumptions and the experimental approaches that established them, and integration of studies conducted in the subtropics led to the following conclusions: Diet does not govern diapause; diapause has not been reported reliably in subtropical and tropical habitats; "reproductive diapause" is a term that presupposes diapause; and diapause should not be determined by a few selected characteristics of poor quality considered alone or in combination with one or two others, including fat bodies and absence of eggs. Overwinter survival modes in the subtropics involve adults feeding on alternative food sources that do not support egg production, quiescent individuals in desiccated bolls, and adults breeding on volunteer cotton plants and their progeny. Resemblance of effects of nutrient deficiencies to frequently used diapause criteria and the roles of subtropical nonreproductive host plants (plants providing sustenance but not suitable for egg development or oviposition), notably cultivated citrus, during winter are discussed.

Unusual brain composition in Crested Ducks ( Anas platyrhynchos f.d.)—Including its effect on behavior and genetic transmission

Crested Ducks (CR) occasionally show intracranial fat bodies. Additionally, behavioral abnormalities such as motor incoordination can be observed. Here, it is shown that a behavioral test helps to identify CR that have a problematical fat body. The ducks were put on their backs, and the time required for them to stand up was measured. Ten CR exhibited suboptimal motor coordination. The appropriateness of this test has been proved in a special breeding program. To investigate the influence of fat bodies on brain composition, an allometrical comparison of 26 CR brains with those of three uncrested duck breeds was done. The fat bodies of CR varied from 0.3% to 41% of total brain volume, but two CR did not show a fat body. CR with motor incoordination show significantly larger fat bodies and require significantly more time in the test than “normal” CR. Total brain volume was significantly larger in CR, but brain volume minus fat body was significantly smaller compared to reference breeds. Cerebellum, apical hyperpallium, tegmentum and olfactory bulb are significantly reduced in CR. Obviously the behavioral deficits cannot be explained by the existence of a fat body, but they could be explained by functionally suboptimal cerebella and tegmenta. Fat body size seems to be a decisive factor. The relationship between fat body and reduced structures is discussed. By breeding with test-selected ducks the hatching rate increased and the number of ducklings with malformations or motor incoordination decreased.

Association of adipose tissue deposition and beta-2 adrenergic receptor variants: the IRAS family study

Adipose tissue distribution (visceral vs subcutaneous) has been shown to be an important predictor of insulin resistance, diabetes and cardiovascular disease, independent of body mass index. The beta-2 adrenergic receptor is a major lipolytic receptor in human fat cells and the gene that codes for this protein is an important candidate gene for measures of adiposity and fat deposition. We examined whether two common polymorphisms in codons 16 (Arg16Gly) and 27 (Gln27Glu) are associated with measures of fat distribution in participants of the IRAS Family Study. We recruited African-American (AA) and Hispanic-American (HA) families from Los Angeles, CA, USA (18 pedigrees, 272 AA individuals), San Antonio, TX, USA (33 pedigrees, 448 HA individuals) and San Luis Valley, CO, USA (12 pedigrees, 272 HA individuals). We estimated adipose tissue distribution via computed tomography. To test for an association between adiposity measures and these polymorphisms, we used generalized estimating equations, adjusting for age, gender, clinical site (ethnicity), body mass index, and familial correlation. Of the 992 individuals genotyped for these polymorphisms, 57% were female and 15% had been diagnosed with type 2 diabetes mellitus. The mean age was 42.7+/-14.6 y. The Glu27 allele of the Gln27Glu polymorphism was positively associated with (P-value for recessive model): body mass index (0.025), visceral adipose tissue (<0.0001) and visceral-to-subcutaneous adipose ratio (0.009), but not with subcutaneous adipose tissue (0.952). The Arg16Gly polymorphism was not associated with any of the adiposity measures. These findings suggest that genetic variation in the beta-2 adrenergic receptor gene influences fat deposition and body size in AAs and HAs. In particular, these results support a role for the gene in the distribution of visceral adipose tissue but not subcutaneous adipose tissue.

Relevance of NAC-2, an Na+-coupled citrate transporter, to life span, body size and fat content in Caenorhabditis elegans.

We have cloned and functionally characterized an Na+-coupled citrate transporter from Caenorhabditis elegans (ceNAC-2). This transporter shows significant sequence homology to Drosophila Indy and the mammalian Na+-coupled citrate transporter NaCT (now known as NaC2). When heterologously expressed in a mammalian cell line or in Xenopus oocytes, the cloned ceNAC-2 mediates the Na+-coupled transport of various intermediates of the citric acid cycle. However, it transports the tricarboxylate citrate more efficiently than dicarboxylates such as succinate, a feature different from that of ceNAC-1 (formerly known as ceNaDC1) and ceNAC-3 (formerly known as ceNaDC2). The transport process is electrogenic, as evidenced from the substrate-induced inward currents in oocytes expressing the transporter under voltage-clamp conditions. Expression studies using a reporter-gene fusion method in transgenic C. elegans show that the gene is expressed in the intestinal tract, the organ responsible for not only the digestion and absorption of nutrients but also for the storage of energy in this organism. Functional knockdown of the transporter by RNAi (RNA interference) not only leads to a significant increase in life span, but also causes a significant decrease in body size and fat content. The substrates of ceNAC-2 play a critical role in metabolic energy production and in the biosynthesis of cholesterol and fatty acids. The present studies suggest that the knockdown of these metabolic functions by RNAi is linked to an extension of life span and a decrease in fat content and body size.