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

OBJECTIVES: This study evaluates the effect of a 3-month calorie restriction (CR) without snacking on the anthropometric parameters, Homeostatic Model Assesment of Insulin Resistance (HOMA-IR), and lipid profiles of female office workers with overweight or obesity, whose physical activity was limited during the COVID-19 pandemic lockdown. MATERIAL AND METHODS: Forty-eight women aged 20-38 years (28.9±5.24) with low physical activity levels were divided into a non-snacking (NS) group (N = 21) and a snacking (S) group (N = 27) prior to the dietary intervention. Their daily energy intake during the intervention was lowered by 30% compared with the baseline level, and the proportion of polyunsaturated fatty acids and fiber in their diet was increased (to >30 g/day). The proportion of saturated fatty acids and simple carbohydrates was also reduced. The study participants were assessed at the baseline and post-intervention for anthropometric variables (body weight, body fat percentage BMI, waist circumference, hip circumference, waist-to-hip ratio) and the concentrations of insulin, total cholesterol (TC), triglycerides (TG), low-density lipoprotein cholesterol (LDL-C), and high-density lipoprotein cholesterol (HDL-C). Moreover, the values for HOMA-IR, the atherogenic index of plasma (AIP), and the ratios of TC/HDL-C, TG/HDL-C, and LDL-C/HDL-C were calculated. RESULTS: All anthropometric parameter values obtained post-intervention were lower than the baseline in both groups. The serum insulin concentration and HOMA-IR decreased respectively by an average of 6% and 25% in the NS group and 37% and 45% in the S group. The lipid profiles of all participants improved significantly, with the LDL-C concentration showing a more promising trend in the S group (decrease by 27%) than in the NS group (17%). CONCLUSIONS: The study showed that CR improved the anthropometric parameters, HOMA-IR index, and lipid profiles of all participants. Int J Occup Med Environ Health. 2022;35(6):693-706.

• Klíčová slova
• coronavirus pandemic, insulin resistance, lipid profile, low physical activity level, reduction diet, snacking,
• MeSH
• COVID-19 * MeSH
• HDL-cholesterol MeSH
• index tělesné hmotnosti MeSH
• inzulin MeSH
• inzulinová rezistence * MeSH
• kalorická restrikce MeSH
• kontrola infekčních nemocí MeSH
• LDL-cholesterol MeSH
• lidé MeSH
• nadváha MeSH
• obezita MeSH
• pandemie MeSH
• triglyceridy MeSH
• Check Tag
• lidé MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• HDL-cholesterol MeSH
• inzulin MeSH
• LDL-cholesterol MeSH
• triglyceridy 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

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

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

People with obesity often struggle to maintain their weight loss after a weight loss period. Furthermore, the effect of weight loss on appetite and food preferences remains unclear. Hence this study investigated the effect of weight loss on subjective appetite and food preferences in healthy, overweight and obese volunteers. A subgroup of adult participants (n = 123) from the Diet Obesity and Genes (DiOGenes) study (subgroup A) was recruited from across six European countries. Participants lost ≥8% of initial body weight during an 8-week low calorie diet (LCD). Subjective appetite and food preferences were measured before and after the LCD, in response to a standardized meal test, using visual analogue rating scales (VAS) and the Leeds Food Choice Questionnaire (FCQ). After the LCD, participants reported increased fullness (p < 0.05), decreased desire to eat (p < 0.05) and decreased prospective consumption (p < 0.05) after consuming the test meal. An interaction effect (visit x time) was found for hunger ratings (p < 0.05). Area under the curve (AUC) for hunger, desire to eat and prospective consumption was decreased by 18.1%, 20.2% and 21.1% respectively whereas AUC for fullness increased by 13.9%. Preference for low-energy products measured by the Food Preference Checklist (FPC) decreased by 1.9% before the test meal and by 13.5% after the test meal (p < 0.05). High-carbohydrate and high-fat preference decreased by 11.4% and 16.2% before the test meal and by 17.4% and 22.7% after the meal (p < 0.05). No other effects were observed. These results suggest that LCD induced weight loss decreases the appetite perceptions of overweight volunteers whilst decreasing their preference for high-fat-, high-carbohydrate-, and low-energy products.

• Klíčová slova
• Body weight maintenance, Hunger, LCD, Leeds food choice questionnaire, Visual analogue scale, Weight loss,
• MeSH
• chuť k jídlu * MeSH
• dietní sacharidy aplikace a dávkování   MeSH
• dietní tuky aplikace a dávkování   MeSH
• dospělí MeSH
• energetický příjem MeSH
• hlad MeSH
• hmotnostní úbytek fyziologie   MeSH
• index tělesné hmotnosti MeSH
• jídla MeSH
• kalorická restrikce * MeSH
• lidé středního věku MeSH
• lidé MeSH
• nadváha MeSH
• obezita * dietoterapie   psychologie   MeSH
• plocha pod křivkou MeSH
• preference v jídle * MeSH
• přijímání potravy MeSH
• prospektivní studie MeSH
• redukční dieta * MeSH
• udržení hmotnosti MeSH
• zpráva o sobě MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• randomizované kontrolované studie MeSH
• Geografické názvy
• Evropa MeSH
• Názvy látek
• dietní sacharidy MeSH
• dietní tuky 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

The hallmarks of tumor tissue are not only genetic aberrations but also the presence of metabolic and oxidative stress as a result of hypoxia and lactic acidosis. The stress activates several prosurvival pathways including metabolic remodeling, autophagy, antioxidant response, mitohormesis, and glutaminolysis, whose upregulation in tumors is associated with a poor survival of patients, while their activation in healthy tissue with statins, metformin, physical activity, and natural compounds prevents carcinogenesis. This review emphasizes the dual role of stress response pathways in cancer and suggests the integrative understanding as a basis for the development of rational therapy targeting the stress response.

• Klíčová slova
• AMPK, Cancer, HIF1α, HO-1, Metabolism, Nrf2, Oxidative stress, PGC1α, Sirtuins,
• MeSH
• antioxidancia metabolismus   MeSH
• autofagie MeSH
• cvičení MeSH
• fyziologický stres fyziologie   MeSH
• hormeze MeSH
• kalorická restrikce MeSH
• lidé MeSH
• mutageneze MeSH
• nádory etiologie   prevence a kontrola   terapie   MeSH
• oxidační stres MeSH
• polyfenoly farmakologie   MeSH
• zánět komplikace   metabolismus   MeSH
• zvířata MeSH
• Check Tag
• lidé MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• přehledy MeSH
• Názvy látek
• antioxidancia MeSH
• polyfenoly MeSH

The purpose of this study was to compare the effects of short-term fasting-induced rapid weight loss with those of slower but equivalent body weight loss induced by daily calorie restriction on muscle protein degradation pathways and muscle protein content. Male Fischer rats were subjected to either 30 % calorie restriction for 2 weeks to slowly decrease body weight (Slow) or 3-day fasting to rapidly decrease body weight by a comparable level of that of the Slow group (Rapid). The final body weights were about 15 % lower in both the Slow and Rapid groups than in the Con group (p<0.001). The total protein content and wet weight of fast-twitch plantaris muscle, but not slow-twitch soleus muscle, were significantly lower in the Rapid group compared with the control rats fed ad libitum. Substantial increases in the expression ratio of autophagosomal membrane proteins (LC3-II/-I ratio) and polyubiquitinated protein concentration, used as biomarkers of autophagy-lysosome and ubiquitin-proteasome activities, respectively, were observed in the plantaris muscle of the Rapid group. Moreover, the LC3-II/-I ratio and polyubiquitinated protein concentration were negatively correlated with the total protein content and wet weight of plantaris muscle. These results suggest that short-term fasting-induced rapid body weight loss activates autophagy-lysosome and ubiquitin-proteasome systems more strongly than calorie restriction-induced slower weight reduction, resulting in muscular atrophy in fast-twitch muscle.

• MeSH
• časové faktory MeSH
• hmotnostní úbytek fyziologie   MeSH
• kalorická restrikce metody   trendy   MeSH
• kosterní svaly metabolismus   MeSH
• krysa rodu Rattus MeSH
• omezení příjmu potravy metabolismus   MeSH
• potkani inbrední F344 MeSH
• proteolýza * MeSH
• signální transdukce fyziologie   MeSH
• svalové proteiny metabolismus   MeSH
• tělesná hmotnost fyziologie   MeSH
• zvířata MeSH
• Check Tag
• krysa rodu Rattus MeSH
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• svalové proteiny MeSH

Mitochondrial dysfunction is a potentially important player in the development of insulin resistance and type 2 diabetes mellitus (T2DM). We investigated the changes of mRNA expression of genes encoding main enzymatic complexes of mitochondrial respiratory chain in subcutaneous adipose tissue (SCAT) and peripheral monocytes (PM) of 11 subjects with simple obesity (OB), 16 obese patients with T2DM and 17 healthy lean subjects (C) before and after very low-calorie diet (VLCD) using quantitative real time PCR. At baseline in SCAT, both T2DM and OB group had decreased mRNA expression of all investigated mitochondrial genes with the exception of 2 complex I (NDUFA 12) and complex IV (COX 4/1) enzymes in OB subjects. In contrast, in PM only the expression of complex I enzymes NDUFA 12 and MT-ND5 was reduced in both T2DM and OB subjects along with decreased expression of citrate synthase (CS) in T2DM group. Additionally, T2DM subjects showed reduced activity of pyruvate dehydrogenase and complex IV in peripheral blood elements. VLCD further decreased mRNA expression of CS and complex I (NT-ND5) and II (SDHA) enzymes in SCAT and complex IV (COX4/1) and ATP synthase in PM of T2DM group, while increasing the activity of complex IV in their peripheral blood elements. We conclude that impaired mitochondrial biogenesis and decreased activity of respiratory chain enzymatic complexes was present in SCAT and PM of obese and diabetic patients. VLCD improved metabolic parameters and ameliorated mitochondrial oxidative function in peripheral blood elements of T2DM subjects but had only minor and inconsistent effect on mitochondrial gene mRNA expression in SCAT and PM.

• MeSH
• diabetes mellitus 2. typu krev   dietoterapie   epidemiologie   MeSH
• dospělí MeSH
• kalorická restrikce metody   trendy   MeSH
• leukocyty mononukleární metabolismus   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mitochondrie metabolismus   MeSH
• obezita krev   dietoterapie   epidemiologie   MeSH
• podkožní tuk metabolismus   MeSH
• výsledek terapie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH