Reproduction, Fat Metabolism, and Life Span: What Is the Connection?

Sanford-Burnham Medical Research Institute, Del E. Webb Neuroscience, Aging and Stem Cell Research Center, Development and Aging Program, La Jolla, CA 92037, USA. Electronic address: .
Cell metabolism (Impact Factor: 17.57). 01/2013; 17(1):10-9. DOI: 10.1016/j.cmet.2012.12.003
Source: PubMed


Reduced reproduction is associated with increased fat storage and prolonged life span in multiple organisms, but the underlying regulatory mechanisms remain poorly understood. Recent studies in several species provide evidence that reproduction, fat metabolism, and longevity are directly coupled. For instance, germline removal in the nematode Caenorhabditis elegans promotes longevity in part by modulating lipid metabolism through effects on fatty acid desaturation, lipolysis, and autophagy. Here, we review these recent studies and discuss the mechanisms by which reproduction modulates fat metabolism and life span. Elucidating the relationship between these processes could contribute to our understanding of age-related diseases including metabolic disorders.

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Available from: Hugo Aguilaniu, Nov 23, 2014
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    • "In addition, it is also necessary to consider particular current concepts of an interrelation between lifespan, reproduction, and fat metabolism (Hansen et al., 2013). It is well established that estradiol signaling is centrally connected with reproduction and energy metabolism (Sinchak & Wagner, 2012). "
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    ABSTRACT: Impaired growth is often associated with an extension of lifespan. However, the negative correlation between somatic growth and life expectancy is only true within, but not between, species. This can be observed because smaller species have, as a rule, a shorter lifespan than larger species. In insects and worms, reduced reproductive development and increased fat storage are associated with prolonged lifespan. However, in mammals the relationship between the dynamics of reproductive development, fat metabolism, growth rate, and lifespan are less clear. To address this point, female transgenic mice that were overexpressing similar levels of either intact (D-mice) or mutant insulin-like growth factor-binding protein-2 (IGFBP-2) lacking the Arg-Gly-Asp (RGD) motif (E- mice) were investigated. Both lines of transgenic mice exhibited a similar degree of growth impairment (-9% and -10%) in comparison with wild-type controls (C-mice). While in D-mice, sexual maturation was found to be delayed and life expectancy was significantly increased in comparison with C-mice, these parameters were unaltered in E-mice in spite of their reduced growth rate. These observations indicate that the RGD-domain has a major influence on the pleiotropic effects of IGFBP-2 and suggest that somatic growth and time of sexual maturity or somatic growth and life expectancy are less closely related than thought previously.
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    • "Because VgRNAi reduced reproduction, it may also increase longevity. Nutrient storage, and especially lipid storage, can be important for longevity in C. elegans, Drosophila, and mice (e.g., Wang et al. 2008, reviewed in Hansen et al. 2013). For phytophagous insects fed plant diets instead of artificial diets, however, protein is essential and often limiting for reproduction (Wheeler 1996; Burmester 1999). "
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    ABSTRACT: Reduced reproduction has been shown to increase lifespan in many animals, yet the mechanisms behind this trade-off are unclear. We addressed this question by combining two distinct, direct means of life-extension via reduced reproduction, to test whether they were additive. In the lubber grasshopper, Romalea microptera, ovariectomized (OVX) individuals had a ~20 % increase in lifespan and a doubling of storage relative to controls (Sham operated). Similarly, young female grasshoppers treated with RNAi against vitellogenin (the precursor to egg yolk protein) had increased fat body mass and halted ovarian growth. In this study, we compared VgRNAi to two control groups that do not reduce reproduction, namely buffer injection (Buffer) and injection with RNAi against a hexameric storage protein (Hex90RNAi). Each injection treatment was tested with and without ovariectomy. Hence, we tested feeding, storage, and lifespans in six groups: OVX and Buffer, OVX and Hex90RNAi, OVX and VgRNAi, Sham and Buffer, Sham and Hex90RNAi, and Sham and VgRNAi. Ovariectomized grasshoppers and VgRNAi grasshoppers each had similar reductions in feeding (~40 %), increases in protein storage in the hemolymph (150-300 %), and extensions in lifespan (13-21 %). Ovariectomized grasshoppers had higher vitellogenin protein levels than did VgRNAi grasshoppers. Last but not least, when ovariectomy and VgRNAi were applied together, there was no greater effect on feeding, protein storage, or longevity. Hence, feeding regulation, and protein storage in insects, may be conserved components of life-extension via reduced reproduction.
    No preview · Article · Aug 2015 · Biogerontology
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    • "Resetting of anatomical or metabolic features of internal organs may thus be a broadly used strategy to achieve a positive energy balance which, when matched to the developing offspring's demands, will contribute to reproductive success. However, if deployed in the absence of such demands, organ remodelling could contribute to the weight gain and increased fat mass that has been observed upon gonadectomy of multiple species including mice, rats, cats, monkeys, and other mammals (Hansen et al., 2013 and references therein). In a more physiological context, inappropriate persistence of such metabolic remodelling beyond pregnancy and lactation could similarly contribute to post-pregnancy weight retention in humans—a phenotype that, at least in mice, is correlated with enhanced intestinal function (Casirola and Ferraris, 2003; Gore et al., 2003). "
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    ABSTRACT: eLife digest Producing offspring places extra energy demands on individuals. Female animals—which generally invest more time and resources than the males—need to ensure that sufficient nutrients reach their offspring during pregnancy and lactation. The small intestines of many female animals increase in size during this period, but it is not clear to what extent these changes help to maximise reproduction, or how they are regulated. Reiff, Jacobson, Cognigni, Antonello et al. investigated what happens to the middle section of the gut in female fruit flies after mating. A fly's ‘midgut’ performs a similar role to the small intestine in humans and other mammals. The experiments show that mating increases the numbers of cells in the midgut so that it increases in size. These changes are due to a hormone called ‘juvenile hormone’, which is released after the fly mates. In particular cells of the midgut, juvenile hormone also regulates some genes involved in the metabolism of lipids. If the activity of juvenile hormone is blocked in these cells, the female flies produce fewer eggs. These changes in the midgut still happen in mutant flies that cannot produce eggs and don't increase their food intake after they mate. Therefore, the changes appear to prepare flies for the increased nutritional demands rather than being caused by it. Altogether, these findings reveal that changes in the midgut play an important role in the ability of female fruit flies to reproduce. Similar changes to the gut may also increase reproductive success in humans and other mammals. However, if the changes are maintained after reproduction, it is possible that they may contribute to weight gain and an increased risk of cancer in females after pregnancy. DOI:
    Full-text · Article · Jul 2015 · eLife Sciences
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