ABSTRACT
There has been an intense focus to uncover the molecular mechanisms by which fasting triggers the adaptive cellular responses in the major organs of the body. Here, we show that in mice, hepatic S-adenosylmethionine (SAMe)-the principal methyl donor-acts as a metabolic sensor of nutrition to fine-tune the catabolic-fasting response by modulating phosphatidylethanolamine N-methyltransferase (PEMT) activity, endoplasmic reticulum-mitochondria contacts, ß-oxidation, and ATP production in the liver, together with FGF21-mediated lipolysis and thermogenesis in adipose tissues. Notably, we show that glucagon induces the expression of the hepatic SAMe-synthesizing enzyme methionine adenosyltransferase α1 (MAT1A), which translocates to mitochondria-associated membranes. This leads to the production of this metabolite at these sites, which acts as a brake to prevent excessive ß-oxidation and mitochondrial ATP synthesis and thereby endoplasmic reticulum stress and liver injury. This work provides important insights into the previously undescribed function of SAMe as a new arm of the metabolic adaptation to fasting.
Subject(s)
Liver Neoplasms , S-Adenosylmethionine , Mice , Animals , S-Adenosylmethionine/metabolism , Liver/metabolism , Liver Neoplasms/metabolism , Fasting , Adenosine Triphosphate/metabolism , Methionine Adenosyltransferase/metabolism , Phosphatidylethanolamine N-Methyltransferase/metabolismABSTRACT
Introducción: La diabetes mellitus y el síndrome de apnea-hipopnea del sueño parecen estar relacionados, pero no está bien definido si en los pacientes con ambas enfermedades existe un mayor riesgo de neuropatía periférica. Para ello, realizamos una revisión sistemática.MétodosBúsqueda bibliográfica en 3 bases de datos electrónicas usando una estrategia predefinida y la metodología PRISMA. Solamente se incluyeron estudios originales (cualquier tipo de diseño) y publicados a partir del año 2000 en inglés, francés, portugués o español. Se estableció una escala de calidad de los estudios.ResultadosSe seleccionaron 12 artículos, de los que 6 estudiaban pacientes diabéticos tipo 2. La prevalencia global de síndrome de apnea-hipopnea del sueño fue del 43,7% (1.559/3.564 pacientes). La neuropatía diabética fue más frecuente en los pacientes con síndrome de apnea-hipopnea del sueño en 9 estudios, aunque solo en 4 de manera significativa (60 vs. 27%, p<0,001; 64,5 vs. 36%, p=0,03; 37 vs. 23,4%, p<0,02; 66,6 vs. 0%, p=0,007). En un estudio, la neuropatía diabética fue más frecuente en los pacientes sin síndrome de apnea-hipopnea del sueño (aunque sin significación estadística) y en 2 no se hizo la comparación entre pacientes con/sin síndrome de apnea-hipopnea del sueño.ConclusionesLos resultados observados indican una relación entre diabetes mellitus y síndrome de apnea-hipopnea del sueño en la aparición de neuropatía diabética.
Introduction: Diabetes mellitus and sleep apnoea-hypopnoea syndrome appear to be related, but it is not well defined whether there is an increased risk of peripheral neuropathy in patients with both diseases. For this reason, we conducted a systematic review.MethodsBibliographic search in 3 electronic databases using a predefined strategy and the PRISMA methodology. Only original studies (any type of design) published from 2000 onwards in English, French, Portuguese or Spanish were included. A study quality scale was established.ResultsTwelve articles were selected, of which six studied type 2 diabetic patients. The overall prevalence of sleep apnoea-hypopnoea syndrome was 43.7% (1,559/3,564 patients). Diabetic neuropathy was more frequent in patients with sleep apnoea-hypopnoea syndrome in nine studies, although significantly only in four (60% vs 27%, P<.001; 64.5% vs 36%, P=.03; 37% vs 23.4%, P<.02; 66.6% vs 0%, P=.007). In one study, diabetic neuropathy was more frequent in patients without sleep apnoea-hypopnoea syndrome (although not statistically significant) and in 2 no comparison was made between patients with/without sleep apnoea/hypopnoea syndrome.ConclusionsThe observed results suggest a relationship between diabetes mellitus and sleep apnoea-hypopnoea syndrome in the occurrence of diabetic neuropathy. (AU)
Subject(s)
Humans , Diabetes Mellitus , Diabetic Neuropathies/epidemiology , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiologyABSTRACT
INTRODUCTION: Diabetes mellitus and sleep apnoea-hypopnoea syndrome appear to be related, but it is not well defined whether there is an increased risk of peripheral neuropathy in patients with both diseases. For this reason, we conducted a systematic review. METHODS: Bibliographic search in 3 electronic databases using a predefined strategy and the PRISMA methodology. Only original studies (any type of design) published from 2000 onwards in English, French, Portuguese or Spanish were included. A study quality scale was established. RESULTS: Twelve articles were selected, of which six studied type 2 diabetic patients. The overall prevalence of sleep apnoea-hypopnoea syndrome was 43.7% (1,559/3,564 patients). Diabetic neuropathy was more frequent in patients with sleep apnoea-hypopnoea syndrome in nine studies, although significantly only in four (60% vs 27%, P<.001; 64.5% vs 36%, P=.03; 37% vs 23.4%, P<.02; 66.6% vs 0%, P=.007). In one study, diabetic neuropathy was more frequent in patients without sleep apnoea-hypopnoea syndrome (although not statistically significant) and in 2 no comparison was made between patients with/without sleep apnoea/hypopnoea syndrome. CONCLUSIONS: The observed results suggest a relationship between diabetes mellitus and sleep apnoea-hypopnoea syndrome in the occurrence of diabetic neuropathy.
Subject(s)
Diabetes Mellitus , Diabetic Neuropathies , Sleep Apnea, Obstructive , Diabetic Neuropathies/epidemiology , Humans , Prevalence , Sleep Apnea, Obstructive/complications , Sleep Apnea, Obstructive/diagnosis , Sleep Apnea, Obstructive/epidemiologyABSTRACT
INTRODUCTION: Atrial fibrillation might increase the risk of dementia. We aim to test the hypothesis that dementia could reclassify the actual risk of stroke and death predicted by the CHA2DS2-VASc in patients with atrial fibrillation (AF). METHODS: A prospective study performed in a specific health care area. RESULTS: From our health care area (n = 348,985), throughout 2013, AF was codified in 7,990 (2.08%). Mean age was 76.83 ± 10.5, mean CHA2DS2-VASc = 3.5, 4,056 (50.8%) were females and 287 (3.6%) were diagnosed to have dementia. Patients with dementia were older and presented a higher rate of all the components of the CHA2DS2-VASc-expect vasculopathy. Differences in overall mortality were observed but not in stroke and haemorrhagic events. After propensity score matched analysis, dementia was independently associated with all-cause mortality. Addition of dementia to CHA2DS2-VASc reclassified 7.7 and 16.6% of the cohort with regard to thromboembolic events and death risk respectively. CONCLUSIONS: Patients with dementia presented a more adverse risk profile, with significant differences in all-cause mortality.
Subject(s)
Atrial Fibrillation/epidemiology , Dementia/epidemiology , Thromboembolism/epidemiology , Aged , Aged, 80 and over , Atrial Fibrillation/mortality , Comorbidity , Dementia/mortality , Europe/epidemiology , Female , Humans , Male , Prognosis , Registries , Risk Assessment , Survival Rate , Thromboembolism/mortalityABSTRACT
No disponible
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Humans , Periodicals as Topic/trends , Editorial Policies , Health Information Management/organization & administrationABSTRACT
No disponible
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Humans , Periodicals as Topic/statistics & numerical data , 50230 , Delivery of Health Care/statistics & numerical data , Journal Impact FactorABSTRACT
No disponible
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Humans , Publishing , Periodicals as Topic , Public Health , SpainABSTRACT
No disponible
