Caloric restriction is associated with a decreased level of oxidative stress. Reactive oxygen species (ROS) generated predominantly in mitochondria are attenuated by decreased caloric intake. On the other hand, antioxidative mechanisms are frequently accelerated by increased gene expression or activities of antioxidant enzymes (superoxide dismutase, catalase, glutathione peroxidase, paraoxonase, etc.). Measurement of different oxidative stress markers in relationship to caloric restriction is therefore important in experimental as well as clinical studies. Estimation of ROS in tissues and fluids is typically performed by measurement of oxidant products (i.e., malondialdehyde, F-2-isoprostanes, nitrotyrosine) and markers of antioxidant system (enzymes, glutathione, alpha-tocopherol, ascorbic acid, ubichinone, etc.). Because both components are critical to objectively understand the oxidative stress state, tangible biochemical data is required in order to comprehensively elucidate pathobiologic mechanisms and potential therapeutic regimes involving lifestyle changes that include caloric restriction or moderate physical activity.

• MeSH
• biologické markery analýza   MeSH
• kalorická restrikce * MeSH
• lidé MeSH
• Check Tag
• lidé MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• biologické markery MeSH

The capacity of cells and organisms to sustain, and to eventually adapt to, environmental and genetic insults declines with age. Because macroautophagy/autophagy is regarded as one of the major determinants of cellular fitness in vitro and in vivo, maneuvers that aim at promoting autophagy may slow down aging and promote health span. Caloric restriction (CR), a reduction in caloric intake without malnutrition, efficiently counteracts aging-associated features, yet is difficult to be applied to humans. Caloric-restriction mimetics (CRMs) are pharmacological agents that recapitulate the main biochemical properties of CR, namely a global reduction of protein acetylation and the induction of autophagy. We found that the ancient drug aspirin and its active metabolite salicylate stimulate autophagic flux by virtue of their inhibitory action on acetyltransferase EP300. The inhibition of EP300 results from a direct competition between salicylate and acetyl coenzyme A for binding to the catalytic domain of the enzyme. This mode of action appears to be conserved across evolution as it accounts for the induction of autophagy by aspirin in various mouse models and in the nematode Caenorhabditis elegans. In sum, aspirin acts as a CRM.

• Klíčová slova
• AMPK, Acetylation, aging, autophagy, fasting, inflammation, longevity, mitophagy, salicylate,
• MeSH
• acetylkoenzym A MeSH
• Aspirin MeSH
• autofagie * MeSH
• Caenorhabditis elegans MeSH
• kalorická restrikce * MeSH
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• komentáře MeSH
• práce podpořená grantem MeSH
• Názvy látek
• acetylkoenzym A MeSH
• Aspirin MeSH

The age-associated deterioration in cellular and organismal functions associates with dysregulation of nutrient-sensing pathways and disabled autophagy. The reactivation of autophagic flux may prevent or ameliorate age-related metabolic dysfunctions. Non-toxic compounds endowed with the capacity to reduce the overall levels of protein acetylation and to induce autophagy have been categorized as caloric restriction mimetics (CRMs). Here, we show that aspirin or its active metabolite salicylate induce autophagy by virtue of their capacity to inhibit the acetyltransferase activity of EP300. While salicylate readily stimulates autophagic flux in control cells, it fails to further increase autophagy levels in EP300-deficient cells, as well as in cells in which endogenous EP300 has been replaced by salicylate-resistant EP300 mutants. Accordingly, the pro-autophagic activity of aspirin and salicylate on the nematode Caenorhabditis elegans is lost when the expression of the EP300 ortholog cpb-1 is reduced. Altogether, these findings identify aspirin as an evolutionary conserved CRM.

• Klíčová slova
• EP300, acetylation, aging, autophagy, longevity, metabolome, salicylate,
• MeSH
• acetylkoenzym A metabolismus   MeSH
• Aspirin farmakologie   MeSH
• autofagie účinky léků   genetika   MeSH
• kalorická restrikce * MeSH
• lidé MeSH
• metabolom účinky léků   MeSH
• metabolomika MeSH
• myši inbrední C57BL MeSH
• nádorové buněčné linie MeSH
• protein p300 asociovaný s E1A metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• acetylkoenzym A MeSH
• Aspirin MeSH
• EP300 protein, human MeSH Prohlížeč
• protein p300 asociovaný s E1A MeSH

Previous studies on various vertebrates have shown that quantity and quality of food intake affect odour attractiveness as perceived by potential mates. In humans, the quality of body odour is similarly affected by ingested foods, such as by variation in meat and garlic intake. Nevertheless, it is not known whether quantity of food has an impact on human body odour attractiveness. Thus, here we tested how 48 h of complete caloric intake restriction affects the hedonic quality of human axillary odour. Odour samples (cotton pads fixed in both armpits and worn for 12 h) were obtained from healthy female donors across three conditions: i) during their habitual food regime; ii) after 48 h of complete caloric intake restriction (drinking water was provided), and iii) 72 h after restoration of caloric intake. Axillary samples were assessed by male raters regarding their pleasantness, attractiveness, femininity, and intensity. We also collected blood samples to assess physiological changes due to dietary restriction (e.g., glucose, sodium, albumin, and triacylglyceride assays) and anthropometric measurements at the same intervals as body odour samples. We found no differences in pleasantness, attractiveness and intensity between the odour samples collected at baseline and during complete caloric intake restriction. Interestingly, we found that body odours were rated more pleasant, more attractive and less intense after restoration of food intake as compared to the baseline and during caloric restriction. Our results suggest that restoration of food intake positively influences hedonic quality of human body odour which might thus provide cues to current fitness status and metabolic efficiency.

• Klíčová slova
• Affective states, BMI, Diet, Fasting, Olfaction, Smell,
• MeSH
• afekt MeSH
• antropometrie MeSH
• dospělí MeSH
• index tělesné hmotnosti MeSH
• kalorická restrikce * MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• odoranty * MeSH
• přijímání potravy MeSH
• složení těla MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH

Caloric restriction mimetics (CRMs) mimic the biochemical effects of nutrient deprivation by reducing lysine acetylation of cellular proteins, thus triggering autophagy. Treatment with the CRM hydroxycitrate, an inhibitor of ATP citrate lyase, induced the depletion of regulatory T cells (which dampen anticancer immunity) from autophagy-competent, but not autophagy-deficient, mutant KRAS-induced lung cancers in mice, thereby improving anticancer immunosurveillance and reducing tumor mass. Short-term fasting or treatment with several chemically unrelated autophagy-inducing CRMs, including hydroxycitrate and spermidine, improved the inhibition of tumor growth by chemotherapy in vivo. This effect was only observed for autophagy-competent tumors, depended on the presence of T lymphocytes, and was accompanied by the depletion of regulatory T cells from the tumor bed.

• Klíčová slova
• cancer, chemotherapy, immunosurveillance, regulatory T cell,
• MeSH
• Atg5 genetika   MeSH
• autofagie MeSH
• citráty aplikace a dávkování   farmakologie   MeSH
• experimentální nádory dietoterapie   farmakoterapie   imunologie   MeSH
• kalorická restrikce metody   MeSH
• lidé MeSH
• methotrexát aplikace a dávkování   farmakologie   MeSH
• monitorování imunologické MeSH
• mutace MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• protoonkogenní proteiny p21(ras) genetika   MeSH
• regulační T-lymfocyty účinky léků   MeSH
• spermidin aplikace a dávkování   farmakologie   MeSH
• transplantace nádorů MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• Atg5 protein, mouse MeSH Prohlížeč
• Atg5 MeSH
• citráty MeSH
• Hras protein, mouse MeSH Prohlížeč
• hydroxycitric acid MeSH Prohlížeč
• methotrexát MeSH
• protoonkogenní proteiny p21(ras) MeSH
• spermidin MeSH

Caloric Restriction (CR) has established anti-cancer effects, but its clinical relevance and molecular mechanism remain largely undefined. Here, we investigate CR's impact on several mouse models of Acute Myeloid Leukemias, including Acute Promyelocytic Leukemia, a subtype strongly affected by obesity. After an initial marked anti-tumor effect, lethal disease invariably re-emerges. Initially, CR leads to cell-cycle restriction, apoptosis, and inhibition of TOR and insulin/IGF1 signaling. The relapse, instead, is associated with the non-genetic selection of Leukemia Initiating Cells and the downregulation of double-stranded RNA (dsRNA) sensing and Interferon (IFN) signaling genes. The CR-induced adaptive phenotype is highly sensitive to pharmacological or genetic ablation of LSD1, a lysine demethylase regulating both stem cells and dsRNA/ IFN signaling. CR + LSD1 inhibition leads to the re-activation of dsRNA/IFN signaling, massive RNASEL-dependent apoptosis, and complete leukemia eradication in ~90% of mice. Importantly, CR-LSD1 interaction can be modeled in vivo and in vitro by combining LSD1 ablation with pharmacological inhibitors of insulin/IGF1 or dual PI3K/MEK blockade. Mechanistically, insulin/IGF1 inhibition sensitizes blasts to LSD1-induced death by inhibiting the anti-apoptotic factor CFLAR. CR and LSD1 inhibition also synergize in patient-derived AML and triple-negative breast cancer xenografts. Our data provide a rationale for epi-metabolic pharmacologic combinations across multiple tumors.

• MeSH
• akutní myeloidní leukemie * patologie   MeSH
• histondemethylasy genetika   MeSH
• inzuliny * MeSH
• kalorická restrikce MeSH
• lidé MeSH
• myši MeSH
• nádorové buněčné linie MeSH
• nádorové kmenové buňky patologie   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• myši MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• histondemethylasy MeSH
• inzuliny * MeSH

BACKGROUND: Epidemiologic studies link short sleep duration to obesity and weight gain. Insufficient sleep appears to alter circulating levels of the hormones leptin and ghrelin, which may promote appetite, although the effects of sleep restriction on caloric intake and energy expenditure are unclear. We sought to determine the effect of 8 days/8 nights of sleep restriction on caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. METHODS: We conducted a randomized study of usual sleep vs a sleep restriction of two-thirds of normal sleep time for 8 days/8 nights in a hospital-based clinical research unit. The main outcomes were caloric intake, activity energy expenditure, and circulating levels of leptin and ghrelin. RESULTS: Caloric intake in the sleep-restricted group increased by +559 kcal/d (SD, 706 kcal/d, P=.006) and decreased in the control group by -118 kcal/d (SD, 386 kcal/d, P=.51) for a net change of +677 kcal/d (95% CI, 148-1,206 kcal/d; P=.014). Sleep restriction was not associated with changes in activity energy expenditure (P=.62). No change was seen in levels of leptin (P=.27) or ghrelin (P=.21). CONCLUSIONS: Sleep restriction was associated with an increase in caloric consumption with no change in activity energy expenditure or leptin and ghrelin concentrations. Increased caloric intake without any accompanying increase in energy expenditure may contribute to obesity in people who are exposed to long-term sleep restriction. TRIAL REGISTRATION: ClinicalTrials.gov; No.: NCT01334788; URL: www.clinicaltrials.gov.

• MeSH
• adherence pacienta MeSH
• dospělí MeSH
• energetický metabolismus fyziologie   MeSH
• energetický příjem fyziologie   MeSH
• ghrelin krev   MeSH
• leptin krev   MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• pohybová aktivita fyziologie   MeSH
• spánková deprivace patofyziologie   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé MeSH
• mladiství MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Research Support, N.I.H., Extramural MeSH
• Názvy látek
• ghrelin MeSH
• leptin MeSH

Cardiovascular disease (CVD), which is the leading cause of death worldwide, is strongly affected by diet. Diet can affect CVD directly by modulating the composition of vascular plaques, and indirectly by affecting the rate of aging. This review summarizes research on the relationships of fasting, meal timing, and meal frequency with CVD incidence and progression. Relevant basic research studies, epidemiological studies, and clinical studies are highlighted. In particular, we discuss both intermittent and periodic fasting interventions with the potential to prevent and treat CVD.

• Klíčová slova
• Blood pressure, Caloric restriction, Cardiovascular disease, Fasting, Fasting mimicking diet,
• Publikační typ
• časopisecké články MeSH
• přehledy MeSH

BACKGROUND: The adipose tissue (AT) is a secretory organ producing a wide variety of factors that participate in the genesis of metabolic disorders linked to excess fat mass. Weight loss improves obesity-related disorders. OBJECTIVES: Transcriptomic studies on human AT, and a combination of analyses of transcriptome and proteome profiling of conditioned media from adipocytes and stromal cells isolated from human AT, have led to the identification of apolipoprotein M (apoM) as a putative adipokine. We aimed to validate apoM as novel adipokine, investigate the relation of AT APOM expression with metabolic syndrome and insulin sensitivity, and study the regulation of its expression in AT and secretion during calorie restriction-induced weight loss. METHODS: We examined APOM mRNA level and secretion in AT from 485 individuals enrolled in 5 independent clinical trials, and in vitro in human multipotent adipose-derived stem cell adipocytes. APOM expression and secretion were measured during dieting. RESULTS: APOM was expressed in human subcutaneous and visceral AT, mainly by adipocytes. ApoM was released into circulation from AT, and plasma apoM concentrations correlate with AT APOM mRNA levels. In AT, APOM expression inversely correlated with adipocyte size, was lower in obese compared to lean individuals, and reduced in subjects with metabolic syndrome and type 2 diabetes. Regardless of fat depot, there was a positive relation between AT APOM expression and systemic insulin sensitivity, independently of fat mass and plasma HDL cholesterol. In human multipotent adipose-derived stem cell adipocytes, APOM expression was enhanced by insulin-sensitizing peroxisome proliferator-activated receptor agonists and inhibited by tumor necrosis factor α, a cytokine that causes insulin resistance. In obese individuals, calorie restriction increased AT APOM expression and secretion. CONCLUSIONS: ApoM is a novel adipokine, the expression of which is a hallmark of healthy AT and is upregulated by calorie restriction. AT apoM deserves further investigation as a potential biomarker of risk for diabetes and cardiovascular diseases.

• Klíčová slova
• adipokine, adipose tissue, calorie restriction, diet, glucose homeostasis, insulin resistance, lipocalin, metabolic syndrome, obesity,
• MeSH
• adipokiny genetika   metabolismus   MeSH
• apolipoproteiny M genetika   metabolismus   MeSH
• kalorická restrikce MeSH
• klinické zkoušky jako téma MeSH
• kohortové studie MeSH
• lidé středního věku MeSH
• lidé MeSH
• longitudinální studie MeSH
• obezita dietoterapie   genetika   metabolismus   MeSH
• průřezové studie MeSH
• tukové buňky metabolismus   MeSH
• Check Tag
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Názvy látek
• adipokiny MeSH
• apolipoproteiny M MeSH

Decreasing the dietary intake of methionine exerts robust anti-adiposity effects in rodents but modest effects in humans. Since cysteine can be synthesized from methionine, animal diets are formulated by decreasing methionine and eliminating cysteine. Such diets exert both methionine restriction (MR) and cysteine restriction (CR), that is, sulfur amino acid restriction (SAAR). Contrarily, SAAR diets formulated for human consumption included cysteine, and thus might have exerted only MR. Epidemiological studies positively correlate body adiposity with plasma cysteine but not methionine, suggesting that CR, but not MR, is responsible for the anti-adiposity effects of SAAR. Whether this is true, and, if so, the underlying mechanisms are unknown. Using methionine- and cysteine-titrated diets, we demonstrate that the anti-adiposity effects of SAAR are due to CR. Data indicate that CR increases serinogenesis (serine biosynthesis from non-glucose substrates) by diverting substrates from glyceroneogenesis, which is essential for fatty acid reesterification and triglyceride synthesis. Molecular data suggest that CR depletes hepatic glutathione and induces Nrf2 and its downstream targets Phgdh (the serine biosynthetic enzyme) and Pepck-M. In mice, the magnitude of SAAR-induced changes in molecular markers depended on dietary fat concentration (60% fat >10% fat), sex (males > females), and age-at-onset (young > adult). Our findings are translationally relevant as we found negative and positive correlations of plasma serine and cysteine, respectively, with triglycerides and metabolic syndrome criteria in a cross-sectional epidemiological study. Controlled feeding of low-SAA, high-polyunsaturated fatty acid diets increased plasma serine in humans. Serinogenesis might be a target for treating hypertriglyceridemia.

• Klíčová slova
• aging, caloric restriction, cysteine, metabolic syndrome, methionine, nutrition, sulfur amino acids, triglycerides,
• MeSH
• aminokyseliny sírové * metabolismus   MeSH
• cystein * metabolismus   MeSH
• lidé MeSH
• metabolismus lipidů MeSH
• methionin metabolismus   MeSH
• myši MeSH
• obezita metabolismus   MeSH
• průřezové studie MeSH
• serin metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• mužské pohlaví MeSH
• myši MeSH
• ženské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• aminokyseliny sírové * MeSH
• cystein * MeSH
• methionin MeSH
• serin MeSH