Meal timing and its role in obesity and associated diseases

Meal timing emerges as a crucial factor influencing metabolic health that can be explained by the tight interaction between the endogenous circadian clock and metabolic homeostasis. Mistimed food intake, such as delayed or nighttime consumption, leads to desynchronization of the internal circadian clock and is associated with an increased risk for obesity and associated metabolic disturbances such as type 2 diabetes and cardiovascular diseases. Conversely, meal timing aligned with cellular rhythms can optimize the performance of tissues and organs. In this review, we provide an overview of the metabolic effects of meal timing and discuss the underlying mechanisms. Additionally, we explore factors influencing meal timing, including internal determinants such as chronotype and genetics, as well as external influences like social factors, cultural aspects, and work schedules. This review could contribute to defining meal-timing-based recommendations for public health initiatives and developing guidelines for effective lifestyle modifications targeting the prevention and treatment of obesity and associated metabolic diseases. Furthermore, it sheds light on crucial factors that must be considered in the design of future food timing intervention trials

СОВРЕМЕННЫЕ ТРАНСФОРМАЦИИ ЭКОНОМИЧЕСКОГО ПРОСТРАНСТВА РОССИИ И РАЗВИТИЕ СОЦИАЛЬНОЙ ИНФРАСТРУКТУРЫ

The article highlights modern emphases of Russian and foreign research studies on social infrastructure. Trends of changes in the content of the "social infrastructure" concept in Russian realities are considered. Taking into account global post-industrial trends, as well as peculiarities of spatial development of Russia and its regions, the need to transform the content of "social infrastructure" concept is substantiated. The analysis of macro-regional space saturation of the Far East by components of social infrastructure is carried out, their parameters are specified. The urgency of problems considered is determined by the necessity of saturation and consolidation of Russian regional space. Thus, social infrastructure is considered from the standpoint of Russian spatial development as a component of space configuration (saturation and consolidation).The purpose of this article is to highlight relevant attributes of modern social infrastructure from national perspectives of human potential preservation and human capital accumulation, as well as to determine indicators and parameters of social infrastructure state of priority macro-region, the Far East. It is proposed to include in concept of social infrastructure functionally significant and thus relevant to the current stage of national development in the post-industrial period components: human potential preservation and human capital accumulation with an emphasis on consistency. The authors propose classification of social infrastructure according to functional bio-socio-humanitarian criterion. The algorithm of complementarity is formed: indicators of each function correspond to specific statistics. This approach is appropriate for use in order to manage development (saturation) of regional (macro-regional) space, especially the Russian Far East.В статье освещены современные акценты российских и зарубежных исследований социальной инфраструктуры. Рассмотрены тенденции изменения содержания понятия «социальная инфраструктура» в российских реалиях. С учетом глобальных постиндустриальных тенденций, а также особенностей пространственного развития России и ее регионов обоснована необходимость трансформации содержания понятия «социальная инфраструктура». Проведен анализ макрорегиональной пространственной насыщенности Дальнего Востока компонентами социальной инфраструктуры, уточнены их параметры. Актуальность рассматриваемых проблем определяется необходимостью насыщения и консолидации российского регионального пространства. Таким образом, социальная инфраструктура рассматривается с точки зрения пространственного развития России как компонента конфигурации пространства (насыщения и консолидации). Целью данной статьи является выделение актуальных атрибутов современной социальной инфраструктуры с национальных позиций сохранения человеческого потенциала и накопления человеческого капитала, а также определение индикаторов и параметров состояния социальной инфраструктуры приоритетного макрорегиона Дальнего Востока. Предлагается включить в концепцию социальной инфраструктуры функционально значимые и, следовательно, соответствующие текущему этапу национального развития в постиндустриальный период компоненты: сохранение человеческого потенциала и накопление человеческого капитала с акцентом на последовательность. Авторами предложена классификация социальной инфраструктуры по функциональному биосоциально-гуманитарному критерию. Формируется алгоритм взаимодополняемости: показатели каждой функции соответствуют конкретной статистике. Такой подход целесообразно использовать для управления развитием (насыщением) регионального (макрорегионального) пространства, особенно российского Дальнего Востока

a randomized controlled trial

Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism

High Protein Diets Improve Liver Fat and Insulin Sensitivity by Prandial but Not Fasting Glucagon Secretion in Type 2 Diabetes

Glucagon (GCGN) plays a key role in glucose and amino acid (AA) metabolism by increasing hepatic glucose output. AA strongly stimulate GCGN secretion which regulates hepatic AA degradation by ureagenesis. Although increased fasting GCGN levels cause hyperglycemia GCGN has beneficial actions by stimulating hepatic lipolysis and improving insulin sensitivity through alanine induced activation of AMPK. Indeed, stimulating prandial GCGN secretion by isocaloric high protein diets (HPDs) strongly reduces intrahepatic lipids (IHLs) and improves glucose metabolism in type 2 diabetes mellitus (T2DM). Therefore, the role of GCGN and circulating AAs in metabolic improvements in 31 patients with T2DM consuming HPD was investigated. Six weeks HPD strongly coordinated GCGN and AA levels with IHL and insulin sensitivity as shown by significant correlations compared to baseline. Reduction of IHL during the intervention by 42% significantly improved insulin sensitivity [homeostatic model assessment for insulin resistance (HOMA-IR) or hyperinsulinemic euglycemic clamps] but not fasting GCGN or AA levels. By contrast, GCGN secretion in mixed meal tolerance tests (MMTTs) decreased depending on IHL reduction together with a selective reduction of GCGN-regulated alanine levels indicating greater GCGN sensitivity. HPD aligned glucose metabolism with GCGN actions. Meal stimulated, but not fasting GCGN, was related to reduced liver fat and improved insulin sensitivity. This supports the concept of GCGN-induced hepatic lipolysis and alanine- and ureagenesis-induced activation of AMPK by HPD

Diurnal distribution of carbohydrates and fat affects substrate oxidation and adipokine secretion in humans.

BACKGROUND: A diet in which fat is mainly eaten in the morning and carbohydrates mainly in the evening (compared with the reverse order) was recently shown to worsen glycemic control in people with prediabetes. OBJECTIVE: We investigated the effects of these dietary patterns on energy metabolism, and on the daily profiles of circulating lipids, adipokines, and inflammatory markers. DESIGN: In a randomized controlled crossover trial, 29 nonobese men (with normal glucose tolerance, n = 18; or impaired fasting glucose/glucose tolerance, n = 11) underwent 2 isocaloric 4-wk diets: 1) carbohydrate-rich meals until 1330 and fat-rich meals between 1630 and 2200 (HC/HF); or 2) the inverse sequence of meals (HF/HC). During a 12-h clinical investigation day after each intervention period, 2 meal tolerance tests were performed, at 0900 and 1540, respectively. Substrate oxidation and concentrations of circulating lipids, adipokines, and cytokines were assessed pre- and postprandially. The postprandial inflammatory response in leukocytes was analyzed ex vivo. RESULTS: Fasting carbohydrate oxidation decreased (P = 0.004) and lipid oxidation increased (P = 0.012) after the HC/HF diet. Fasting concentrations of blood markers did not differ between diets. The diets modulated the daily profiles of carbohydrate oxidation, lipid oxidation, and β-hydroxybutyrate, although the average daily values of these parameters showed no difference between the diets, and no interaction between diet and glucose tolerance status. Diurnal patterns of triglycerides, low-density lipoprotein cholesterol, leptin, visfatin, and of LPS-induced cytokine secretion in blood leukocytes were also modulated by the diets. Average daily concentrations of leptin (P = 0.017) and visfatin (P = 0.041) were lower on the HF/HC diet than on the HC/HF diet. CONCLUSIONS: Diurnal distribution of carbohydrates and fat affects the daily profiles of substrate oxidation, circulating lipids, and cytokine secretion, and alters the average daily concentrations of adipokine secretion in nonobese nondiabetic humans. The study was registered at clinicaltrials.gov as NCT02487576

The effect of diurnal distribution of carbohydrates and fat on glycaemic control in humans: a randomized controlled trial.

Diurnal carbohydrate and fat distribution modulates glycaemic control in rodents. In humans, the optimal timing of both macronutrients and its effects on glycaemic control after prolonged consumption are not studied in detail. In this cross-over trial, 29 non-obese men were randomized to two four-week diets: (1) carbohydrate-rich meals until 13.30 and fat-rich meals between 16.30 and 22.00 (HC/HF) versus (2) inverse sequence of meals (HF/HC). After each trial period two meal tolerance tests were performed, at 09.00 and 15.40, respectively, according to the previous intervention. On the HF/HC diet, whole-day glucose level was increased by 7.9% (p = 0.026) in subjects with impaired fasting glucose and/or impaired glucose tolerance (IFG/IGT, n = 11), and GLP-1 by 10.2% (p = 0.041) in normal glucose-tolerant subjects (NGT, n = 18). Diet effects on fasting GLP-1 (p = 0.009) and PYY (p = 0.034) levels were observed in IFG/IGT, but not in NGT. Afternoon decline of glucose tolerance was more pronounced in IFG/IGT and associated with a stronger decrease of postprandial GLP-1 and PYY levels, but not with changes of cortisol rhythm. In conclusion, the HF/HC diet shows an unfavourable effect on glycaemic control in IFG/IGT, but not in NGT subjects. Consequently, large, carbohydrate-rich dinners should be avoided, primarily by subjects with impaired glucose metabolism

Slav-NER : the 3rd Cross-lingual Challenge on Recognition, Normalization, Classification, and Linking of Named Entities across Slavic languages

Non peer reviewe

Shotgun Lipidomics Discovered Diurnal Regulation of Lipid Metabolism Linked to Insulin Sensitivity in Nondiabetic Men.

CONTEXT: Meal timing affects metabolic homeostasis and body weight, but how composition and timing of meals affect plasma lipidomics in humans is not well studied. OBJECTIVE: We used high throughput shotgun plasma lipidomics to investigate effects of timing of carbohydrate and fat intake on lipid metabolism and its relation to glycemic control. DESIGN: 29 nondiabetic men consumed (1) a high-carb test meal (MTT-HC) at 09.00 and a high-fat meal (MTT-HF) at 15.40; or (2) MTT-HF at 09.00 and MTT-HC at 15.40. Blood was sampled before and 180 minutes after completion of each MTT. Subcutaneous adipose tissue (SAT) was collected after overnight fast and both MTTs. Prior to each investigation day, participants consumed a 4-week isocaloric diet of the same composition: (1) high-carb meals until 13.30 and high-fat meals between 16.30 and 22:00 or (2) the inverse order. RESULTS: 12 hour daily lipid patterns showed a complex regulation by both the time of day (67.8%) and meal composition (55.4%). A third of lipids showed a diurnal variation in postprandial responses to the same meal with mostly higher responses in the morning than in the afternoon. Triacylglycerols containing shorter and more saturated fatty acids were enriched in the morning. SAT transcripts involved in fatty acid synthesis and desaturation showed no diurnal variation. Diurnal changes of 7 lipid classes were negatively associated with insulin sensitivity, but not with glucose and insulin response or insulin secretion. CONCLUSIONS: This study identified postprandial plasma lipid profiles as being strongly affected by meal timing and associated with insulin sensitivity

Orphan GPR116 mediates the insulin sensitizing effects of the hepatokine FNDC4 in adipose tissue

The proper functional interaction between different tissues represents a key component in systemic metabolic control. Indeed, disruption of endocrine inter-tissue communication is a hallmark of severe metabolic dysfunction in obesity and diabetes. Here, we show that the FNDC4-GPR116, liver-white adipose tissue endocrine axis controls glucose homeostasis. We found that the liver primarily controlled the circulating levels of soluble FNDC4 (sFNDC4) and lowering of the hepatokine FNDC4 led to prediabetes in mice. Further, we identified the orphan adhesion GPCR GPR116 as a receptor of sFNDC4 in the white adipose tissue. Upon direct and high affinity binding of sFNDC4 to GPR116, sFNDC4 promoted insulin signaling and insulin-mediated glucose uptake in white adipocytes. Indeed, supplementation with FcsFNDC4 in prediabetic mice improved glucose tolerance and inflammatory markers in a white-adipocyte selective and GPR116-dependent manner. Of note, the sFNDC4-GPR116, liver-adipose tissue axis was dampened in (pre) diabetic human patients. Thus our findings will now allow for harnessing this endocrine circuit for alternative therapeutic strategies in obesity-related pre-diabetes. The soluble bioactive form of the transmembrane protein fibronectin type III domain containing 4 (sFNDC4) has anti-inflammatory effects and improves insulin sensitivity. Here the authors show that liver derived sFNDC4 signals through adipose tissue GPCR GPR116 to promote insulin-mediated glucose uptake.Peer reviewe

Kardiovaskuläre, inflammatorische und zirkadiane Aspekte der Stoffwechselregulation bei Menschen

Obesity and associated metabolic disorders are an epidemic and still growing health problem of ”Western lifestyle” countries including Germany. Many important pathophysiological aspects of metabolic disturbances remain poorly understood. The present work describes several new cardiovascular, inflammatory and circadian mechanisms contributing to the human metabolic regulation in health and disease. Firstly, the role of insulin clearance in the pathophysiology of metabolic syndrome was characterized. The decreased insulin clearance is an early marker of insulin metabolism disturbances. We demonstrated that hepatic insulin clearance is associated with several components of metabolic syndrome such as waist circumference, plasma triglycerides, diastolic blood pressure, fasting glucose, and markers of insulin secretion and insulin sensitivity. Therefore, decreased insulin clearance could be additionally applied for early identification of subjects with high risk of metabolic syndrome. Secondly, we investigated mechanisms of natriuretic peptide regulation in obesity. Natriuretic peptides ANP, BNP and CNP show cardioprotective effects and their circulating levels are reduced in obesity. We found that insulin increases expression of natriuretic peptide clearance receptor (NPRC) in subcutaneous adipose tissue and decreases circulating levels of midregional proANP (MR-proANP) independently of circulating glucose concentrations. Accordingly, insulin may reduce natriuretic peptide levels in circulation via up-regulation of NPRC expression providing a new link between hyperinsulinemia and cardiovascular diseases. Thirdly, novel nutrition-dependent mechanisms contributing to the progression of the adipose tissue inflammation were characterized. We showed that human monocytes and macrophages express a panel of nutrition-associated receptors (GPR41, GPR43, GIPR, GLP1R etc.) suggesting that an activation of corresponding signaling may regulate the low-grade inflammation in adipose tissue. Furthermore, a WNT-inducible signaling pathway protein-1 (WISP1) was validated as a novel human adipokine which is released by adipocytes and stimulates cytokine responses in macrophages. Hence, WISP1 may contribute to the link between obesity, inflammation and insulin resistance. Finally, the applicant’s research highlighted the importance of circadian clock in human metabolic responses to food intake. We found that dietary fat and carbohydrate content alters peripheral clock oscillations in blood monocytes and the rhythm of cortisol, a central clock marker. The network analysis showed numerous correlation links between clock genes and metabolic and inflammatory pathways in blood monocytes confirming the tight crosstalk between clock and metabolism in humans. Thus, the research work of the applicant elucidated a range of novel pathophysiological aspects of metabolic regulation in humans and identified new promising targets for the prevention and treatment of metabolic diseases.Adipositas und assoziierte metabolische Erkrankungen stellen ein immer noch wachsendes gesundheitliches Problem in westlichen Ländern einschließlich Deutschland dar. Viele pathophysiologische Aspekte der metabolischen Regulation bei Menschen sind noch unbekannt. Die vorgelegte Arbeit beschreibt einige neue kardiovaskuläre, inflammatorische und zirkadiane Mechanismen der physiologischen und pathophysiologischen Regulation des humanen Stoffwechsels. Als Erstes haben wir die Rolle der hepatischen Insulinclearance beim Metabolischen Syndrom untersucht. Verminderte Insulinclearance ist ein früher Marker der Störungen des Insulinstoffwechsels. Wir haben nachgewiesen, dass die verminderte Insulinclearance stark mit Parametern des Metabolischen Syndroms assoziiert ist, inklusive Tailienumfang, Plasma-Triglyzeride, diastolischem Blutdruck, nüchternem Glucosespiegel, sowie mit Indizes der Insulinsekretion und Insulinsensitivität. Demgemäß kann die verminderte Insulinclearance einen neuen pathophysiologischen Mechanismus des Metabolischen Syndroms darstellen. Als Zweites haben wir die Mechanismen der Regulation der natriuretischen Peptide bei Adipositas untersucht. Natriuretische Peptide wie ANP, BNP und CNP, die eine kardioprotektive Wirkung haben, sind bei Adipositas vermindert. Wir haben nachgewiesen, dass eine Insulin-Infusion die Expression des Natriuretic Peptide Clearance Receptors (NPRC) in subkutanem Fettgewebe der adipösen Probanden akut erhöht und den Plasmaspiegel des Midregionalen proANPs (MR-proANP) unabhängig von der Glukosekonzentration reduziert. Diese Insulin-induzierte Regulation der NPRC- Expression könnte zur Senkung der natriuretischen Peptide im Blut bei Adipositas führen und ein neuen Zusammenhang zwischen Hyperinsulinämie und kardiovaskulären Komponenten darstellen. Als Drittes wurden neue Mechanismen der chronischen Adipositas-assoziierten Entzündung im Fettgewebe charakterisiert. Wir haben die Expression zahlreicher „ernährungsassoziierten“ Rezeptoren (GPR41, GPR43, GIPR, GLP1R usw.) in humanen Blutmonozyten und Makrophagen nachgewiesen, deren Aktivierung bei der Regulation der Entzündung im Fettgewebe beitragen könnte. Des Weiteren wurde das WNT-Inducible Signaling Pathway Protein-1 (WISP1) als neues humanes Adipokin charakterisiert, das von Adipozyten ausgeschüttet wird und die Sekretion proinflammatorischer Zytokine in Makrophagen stimuliert. Demgemäß könnte WISP1 eine neue molekulare Verbindung zwischen Adipositas, Fettgewebsentzündung und Insulinresistenz darstellen. Die vorliegende Arbeit betont auch die Bedeutung der zirkadianen Uhr in der Regulation der metabolischen Antwort auf die Nahrungsaufnahme. Wir haben entdeckt, dass der Kohlenhydrat- und Fettanteil der Diät die Oszillationen der peripheren Uhrgene in Blutmonozyten und den Rhythmus von Cortisol, den Marker der zentralen Uhr, beeinflusst. Eine Netzwerkanalyse hat zahlreiche Korrelationen der Uhrgene mit Markern der Inflammation und des Fettstoffwechsels gezeigt und die feste Interaktion zwischen innerer Uhr und Stoffwechsel bei Menschen bestätigt. Zusammenfassend demonstriert die vorgelegte Arbeit eine Reihe neuer pathophysiologischer Aspekte der Stoffwechselregulation bei Menschen und identifiziert neue vielversprechende Targets für die Vorbeugung und Behandlung von Stoffwechselerkrankungen