Caloric restriction (CR) reduces the risk of age-related diseases in numerous species, including humans. CR's metabolic effects, including decreased adiposity and improved insulin sensitivity, are ...important for its broader health benefits; however, the extent and basis of sex differences in CR's health benefits are unknown. We found that 30% CR in young (3-month-old) male mice decreased fat mass and improved glucose tolerance and insulin sensitivity, whereas these effects were blunted or absent in young females. Females' resistance to fat loss was associated with decreased lipolysis, energy expenditure and fatty acid oxidation, and increased postprandial lipogenesis, compared to males. The sex differences in glucose homeostasis were not associated with differential glucose uptake but with altered hepatic ceramide content and substrate metabolism: compared to CR males, CR females had lower TCA cycle activity and higher blood ketone concentrations, a marker of hepatic acetyl-CoA content. This suggests that males use hepatic acetyl-CoA for the TCA cycle whereas in females it accumulates, stimulating gluconeogenesis and limiting hypoglycaemia during CR. In aged mice (18-months old), when females are anoestrus, CR decreased fat mass and improved glucose homeostasis similarly in both sexes. Finally, in a cohort of overweight and obese humans, CR-induced fat loss was also sex- and age-dependent: younger females (<45 years) resisted fat loss compared to younger males while in older subjects (>45 years) this sex difference was absent. Collectively, these studies identify age-dependent sex differences in the metabolic effects of CR and highlight adipose tissue, the liver and oestrogen as key determinants of CR's metabolic benefits. These findings have important implications for understanding the interplay between diet and health, and for maximising the benefits of CR in humans.
Countless millions of people have died from tuberculosis, a chronic infectious disease caused by the tubercle bacillus. The complete genome sequence of the best-characterized strain of Mycobacterium ...tuberculosis, H37Rv, has been determined and analysed in order to improve our understanding of the biology of this slow-growing pathogen and to help the conception of new prophylactic and therapeutic interventions. The genome comprises 4,411,529 base pairs, contains around 4,000 genes, and has a very high guanine + cytosine content that is reflected in the biased amino-acid content of the proteins. M. tuberculosis differs radically from other bacteria in that a very large portion of its coding capacity is devoted to the production of enzymes involved in lipogenesis and lipolysis, and to two new families of glycine-rich proteins with a repetitive structure that may represent a source of antigenic variation.
Bone marrow adipose tissue (MAT) contributes to increased circulating adiponectin, an insulin-sensitizing hormone, during caloric restriction (CR), but whether this occurs in other contexts remains ...unknown. The antidiabetic thiazolidinediones (TZDs) also promote MAT expansion and hyperadiponectinemia, even without increasing adiponectin expression in white adipose tissue (WAT).
To test the hypothesis that MAT expansion contributes to TZD-associated hyperadiponectinemia, we investigated the effects of rosiglitazone, a prototypical TZD, in wild-type (WT) or
-Wnt10b mice. The latter resist MAT expansion during CR, leading us to postulate that they would also resist this effect of rosiglitazone.
Male and female WT or
-Wnt10b mice (C57BL/6J) were treated with or without rosiglitazone for 2, 4, or 8 weeks, up to 30 weeks of age. MAT content was assessed by osmium tetroxide staining and adipocyte marker expression. Circulating adiponectin was determined by ELISA.
In WT mice, rosiglitazone caused hyperadiponectinemia and MAT expansion. Compared to WT mice,
-Wnt10b mice had significantly less MAT in distal tibiae and sometimes in proximal tibiae; however, interpretation was complicated by the leakage of osmium tetroxide from ruptures in some tibiae, highlighting an important technical consideration for osmium-based MAT analysis. Despite decreased MAT in
Wnt10b mice, circulating adiponectin was generally similar between WT and
-Wnt10b mice; however, in females receiving rosiglitazone for 4 weeks, hyperadiponectinemia was significantly blunted in
Wnt10b compared to WT mice. Notably, this was also the only group in which tibial adiponectin expression was lower than in WT mice, suggesting a close association between MAT adiponectin production and circulating adiponectin. However, rosiglitazone significantly increased adiponectin protein expression in WAT, suggesting that WAT contributes to hyperadiponectinemia in this context. Finally, rosiglitazone upregulated uncoupling protein 1 in brown adipose tissue (BAT), but this protein was undetectable in tibiae, suggesting that MAT is unlikely to share thermogenic properties of BAT.
TZD-induced hyperadiponectinemia is closely associated with increased adiponectin production in MAT but is not prevented by the partial loss of MAT that occurs in
Wnt10b mice. Thus, more robust loss-of-MAT models are required for future studies to better establish MAT's elusive functions, both on an endocrine level and beyond.
White adipose tissue (WAT) is a major endocrine organ, secreting a diverse range of hormones, lipid species, cytokines and other factors to exert diverse local and systemic effects. These secreted ...products, known as ‘adipokines’, contribute extensively to WAT’s impact on physiology and disease. Adipocytes also exist in the bone marrow (BM), but unlike WAT, study of this bone marrow adipose tissue (MAT) has been relatively limited. We recently discovered that MAT contributes to circulating adiponectin, an adipokine that mediates cardiometabolic benefits. Moreover, we found that MAT expansion exerts systemic effects. Together, these observations identify MAT as an endocrine organ. Additional studies are revealing further secretory functions of MAT, including production of other adipokines, cytokines and lipids that exert local effects within bone. These observations suggest that, like WAT, MAT has secretory functions with diverse potential effects, both locally and systemically. A major limitation is that these findings are often based on in vitro approaches that may not faithfully recapitulate the characteristics and functions of BM adipocytes in vivo. This underscores the need to develop improved methods for in vivo analysis of MAT function, including more robust transgenic models for MAT targeting, and continued development of techniques for non-invasive analysis of MAT quantity and quality in humans. Although many aspects of MAT formation and function remain poorly understood, MAT is now attracting increasing research focus; hence, there is much promise for further advances in our understanding of MAT as an endocrine organ, and how MAT impacts human health and disease.
Analysis of Plasmodium falciparum chromosome 3, and comparison with chromosome 2, highlights novel features of chromosome organization and gene structure. The sub-telomeric regions of chromosome 3 ...show a conserved order of features, including repetitive DNA sequences, members of multigene families involved in pathogenesis and antigenic variation, a number of conserved pseudogenes, and several genes of unknown function. A putative centromere has been identified that has a core region of about 2 kilobases with an extremely high (adenine + thymidine) composition and arrays of tandem repeats. We have predicted 215 protein-coding genes and two transfer RNA genes in the 1,060,106-base-pair chromosome sequence. The predicted protein-coding genes can be divided into three main classes: 52.6% are not spliced, 45.1% have a large exon with short additional 5' or 3' exons, and 2.3% have a multiple exon structure more typical of higher eukaryotes.
Celotno besedilo
Dostopno za:
DOBA, IJS, IZUM, KILJ, NUK, PILJ, PNG, SAZU, SIK, UILJ, UKNU, UL, UM, UPUK
We have generated over 100 kilobases of sequence from the nonrecombining portion of the Y chromosomes from five humans and one common chimpanzee. The human subjects were chosen to match the earliest ...branches of the human mitochondrial tree. The survey of 18.3 kilobases from each human detected only three sites at which substitutions were present, whereas the human and chimpanzee sequences showed 1.3% divergence. The coalescence time estimated from our Y chromosome sample is more recent than that of the mitochondrial genome. A recent coalescence time for the Y chromosome could have been caused by the selected sweep of an advantageous Y chromosome or extensive migration of human males.
The Genome of Caenorhabditis elegans Waterston, R.; Sulston, J.
Proceedings of the National Academy of Sciences,
11/1995, Letnik:
92, Številka:
24
Journal Article
Recenzirano
Odprti dostop
The physical map of the 100-Mb Caenorhabditis elegans genome consists of 17,500 cosmids and 3500 yeast artificial chromosomes (YACs). A total of 22.5 Mb has been sequenced, with the remainder ...expected by 1998. A further 15.5 Mb of unfinished sequence is freely available online: because the areas sequenced so far are relatively gene rich, about half the 13,000 genes can now be scanned. More than a quarter of the genes are represented by expressed sequence tags (ESTs). All information pertaining to the genome is publicly available in the ACeDB data base.
As part of our effort to sequence the 100-megabase (Mb) genome of the nematode Caenorhabditis elegans, we have completed the nucleotide sequence of a contiguous 2,181,032 base pairs in the central ...gene cluster of chromosome III. Analysis of the finished sequence has indicated an average density of about one gene per five kilobases; comparison with the public sequence databases reveals similarities to previously known genes for about one gene in three. In addition, the genomic sequence contains several intriguing features, including putative gene duplications and a variety of other repeats with potential evolutionary implications.
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