RESUMO
Common obesity is associated with the metabolic syndrome and can be distinguished from secondary obesity and from rare forms of monogenic and polygenic obesity. The prevalence of common obesity has become a public health concern in many countries as phenomenological approaches to the understanding of obesity have failed to achieve any long term effect on prevention or treatment. There is evidence for a central control mechanism which maintains body-weight to a set-point by the regulation of energy intake and energy expenditure through homeostatic pathways. It is suggested in this paper that common obesity occurs when the set-point is raised and that accumulation of fat mass functions to increase body size. Larger body size confers a survival advantage in the cold ambient temperatures and food scarcity of the winter climate by reducing surface area to volume ratio and by providing an energy store in the form of fat mass. In addition, it is suggested that the phenotypic metabolic and physiological changes observed as the metabolic syndrome, including hypertension and insulin resistance, could result from a winter metabolism which increases thermogenic capacity. Common obesity and the metabolic syndrome may therefore result from an anomalous adaptive winter response. The stimulus for the winter response is proposed to be a fall in vitamin D. The synthesis of vitamin D is dependent upon the absorption of radiation in the ultraviolet-B range of sunlight. At ground level at mid-latitudes, UV-B radiation falls in the autumn and becomes negligible in winter. It has previously been proposed that vitamin D evolved in primitive organisms as a UV-B sensitive photoreceptor with the function of signaling changes in sunlight intensity. It is here proposed that a fall in vitamin D in the form of circulating calcidiol is the stimulus for the winter response, which consists of an accumulation of fat mass (obesity) and the induction of a winter metabolism (the metabolic syndrome). Vitamin D deficiency can account for the secular trends in the prevalence of obesity and for individual differences in its onset and severity. It may be possible to reverse the increasing prevalence of obesity by improving vitamin D status.
Assuntos
Modelos Biológicos , Obesidade/complicações , Obesidade/fisiopatologia , Deficiência de Vitamina D/complicações , Deficiência de Vitamina D/fisiopatologia , Vitamina D/metabolismo , Humanos , Incidência , Obesidade/epidemiologia , Prevalência , Deficiência de Vitamina D/epidemiologiaRESUMO
Human GATA-6 has been cloned from foetal heart by a combination of PCR-based methods and cDNA library screening. The 3.8 kbp cDNA has a coding sequence of 1347 bp the 449 aa protein is virtually identical in the two zinc-finger binding domains to other human GATA sequences, but varies considerably in the amino and carboxy terminal regions. The sequence shows greatest similarity to GATA-6-like sequences from rat, mouse, chicken and Xenopus. Northern analysis and in situ hybridisation show that GATA-6 is expressed at high levels in human adult and foetal heart as well as in gut derivatives. It is postulated that GATA-6, in concert with GATA-4, plays a crucial role in the regulation of cardiac differentiation.
Assuntos
DNA Complementar/biossíntese , Proteínas de Ligação a DNA/biossíntese , Miocárdio/metabolismo , Fatores de Transcrição/biossíntese , Sequência de Aminoácidos , Sequência de Bases , Clonagem Molecular , Sistema Digestório/metabolismo , Feto/metabolismo , Fator de Transcrição GATA6 , Expressão Gênica , Biblioteca Gênica , Humanos , Hibridização In Situ , Dados de Sequência MolecularRESUMO
We describe changes in antigen expression on HL60 cells with differentiation into granulocytes induced by all-trans retinoic acid (ATRA) or dimethylsulphoxide (DMSO), into monocytes by alpha1,25-dihydroxyvitamin D3 (D3), or into macrophages by 12-O-tetradecanoyl phorbol-13-acetate (TPA). Undifferentiated cells expressed CD13, CD14 (at a low level), CD15, CDw17, CD32, CD33, CD49e, CD63, CD64, CDw65, CD71 and CD87 antigens and bound the unclustered mAb D171 and Mo5. Differentiated and undifferentiated cells were negative for CD16, CD34, CD61, CD66abcde, CD68, CD88, CDw90 and CD93. Four panels of markers were identified whose expression changes significantly following differentiation. CD15, CD49e, CD63, CDw65, CD71 and mAb D171 and IGR-2,1A6 for DMSO; CD13, CD15, CDw17, CD49e, CD63, CDw65, CD71, CD87, CDw92 and mAb D171 and IGR-2,1A6 for ATRA; CD14, CD31, CD35, CD71, CD87, CDw92 and mAb D171 and BRIC18 for D3; CDw12, CD13, CD15, CD31, CD35, CD49e, CD71, CD87, CDw92 and mAb D171 for TPA. These will be useful for analyzing the pathways that regulate differentiation, whether the observed changes are consequences of differentiation or more direct effects of the inducers. HL60 cells provide a model for investigating the regulation of these antigens.
Assuntos
Antígenos CD/biossíntese , Antígenos CD/efeitos dos fármacos , Calcitriol/farmacologia , Dimetil Sulfóxido/farmacologia , Células HL-60/citologia , Células HL-60/metabolismo , Acetato de Tetradecanoilforbol/farmacologia , Tretinoína/farmacologia , Diferenciação Celular/efeitos dos fármacos , Células HL-60/efeitos dos fármacos , HumanosAssuntos
Primers do DNA , DNA Complementar/química , Biblioteca Gênica , Reação em Cadeia da Polimerase/métodos , Sequência de Bases , Elementos de DNA Transponíveis , DNA Complementar/síntese química , Expressão Gênica , Vetores Genéticos , Indicadores e Reagentes , Dados de Sequência Molecular , Mutagênese Insercional , Mutagênese Sítio-Dirigida , Sensibilidade e Especificidade , Deleção de SequênciaRESUMO
BACKGROUND & AIMS: Liver-specific membrane lipoprotein (LSP) is a heterogeneous liver preparation that has been widely used to study autoreactivity in liver disease. The aim of this study was to identify autoantigens in LSP. METHODS: Guinea pig anti-LSP serum was used to screen a human liver complementary DNA (cDNA) library. Humoral immune responses to isolated potential autoantigens were investigated by immunoblotting in 91 pediatric patients with various liver diseases, 20 adult patients with alcoholic liver disease and 20 with autoimmune thyroid disease, 37 healthy children, and 20 healthy adults. RESULTS: A 1.6-kilobase cDNA insert isolated from the cDNA library was found to encode amino acids 61-374 of the human alcohol dehydrogenase (ADH)-gamma 1 subunit. Antibodies to this or other ADH subunits were found significantly more frequently in autoimmune liver diseases (19 of 39 patients; 49%), Wilson's disease (5 of 13 patients; 38%), and alcoholic liver disease (10 of 20 patients; 50%) than in normal controls (P < 0.0001, P < 0.005, and P < 0.05, respectively) and correlated with disease activity in autoimmune liver disease. CONCLUSIONS: ADH has been identified as a new antigenic component of the LSP using a xenogeneic antiserum to immunoprobe a human cDNA liver library and seems to be a target autoantigen in liver disease. This approach may be useful in identifying other potential autoantigens.