El ayuno intermitente y sus efectos en la salud metabólica en humanos / Intermittent fasting and human metabolic health

Intermittent fasting (IF) has gained increasing scientific and general attention. Most studied forms of IF include alternate-day fasting, modified alternate-day fasting, and time-restricted eating (TRE). Several cardiometabolic effects of IF have been described in animal models and, to a lesser extent, in humans. This review analyzes the impact of IF on weight loss, glucose metabolism, blood pressure, and lipid profile in humans. A literature search was conducted in the Pubmed/Medline, Scopus, and Google Scholar databases. Controlled observational or interventional studies in humans, published between January 2000 and June 2021, were included. Studies comparing IF versus religious fasting were not included. Most studies indicate that the different types of IF have significant benefits on body composition, inducing weight loss and reducing fat mass. Changes in cardiometabolic parameters show more divergent results. In general, a decrease in fasting glucose and insulin levels is observed, together with an improved lipid profile associated with cardiovascular risk. High heterogeneity in study designs was observed, particularly in studies with TRE, small sample sizes, and short-term interventions. Current evidence shows that IF confers a range of cardiometabolic benefits in humans. Weight loss, improvement of glucose homeostasis and lipid profile, are observed in the three types of IF protocols evaluated.

Role of melatonin receptor 1B gene polymorphism and its effect on the regulation of glucose transport in gestational diabetes mellitus / 浙江大学学报（英文版）（B辑：生物医学和生物技术）

Melatonin receptor 1B (MT2, encoded by the MTNR1B gene), a high-affinity receptor for melatonin, is associated with glucose homeostasis including glucose uptake and transport. The rs10830963 variant in the MTNR1B gene is linked to glucose metabolism disorders including gestational diabetes mellitus (GDM); however, the relationship between MT2-mediated melatonin signaling and a high birth weight of GDM infants from maternal glucose abnormality remains poorly understood. This article aims to investigate the relationship between rs10830963 variants and GDM development, as well as the effects of MT2 receptor on glucose uptake and transport in trophoblasts. TaqMan-MGB (minor groove binder) probe quantitative real-time polymerase chain reaction (qPCR) assays were used for rs10930963 genotyping. MT2 expression in the placenta of GDM and normal pregnant women was detected by immunofluorescence, western blot, and qPCR. The relationship between MT2 and glucose transporters (GLUTs) or peroxisome proliferator-activated receptor γ (PPARγ) was established by western blot, and glucose consumption of trophoblasts was measured by a glucose assay kit. The results showed that the genotype and allele frequencies of rs10830963 were significantly different between GDM and normal pregnant women (P<0.05). The fasting, 1-h and 2-h plasma glucose levels of G-allele carriers were significantly higher than those of C-allele carriers (P<0.05). Besides, the protein and messenger RNA (mRNA) expression of MT2 in the placenta of GDM was significantly higher than that of normal pregnant women (P<0.05). Melatonin could stimulate glucose uptake and GLUT4 and PPARγ protein expression in trophoblasts, which could be attenuated by MT2 receptor knockdown. In conclusion, the rs10830963 variant was associated with an increased risk of GDM. The MT2 receptor is essential for melatonin to raise glucose uptake and transport, which may be mediated by PPARγ.

Hydrogen-rich water reduces cell damage by reducing excessive autophagy in mouse neuronal cells after oxygen glucose deprivation/reoxygenation / 中华危重病急救医学

OBJECTIVE@#To investigate whether hydrogen-rich water exerts a protective effect against cellular injury by affecting the level of autophagy after oxygen glucose deprivation/reoxygenation (OGD/R) in a mouse hippocampal neuronal cell line (HT22 cells).@*METHODS@#HT22 cells in logarithmic growth phase were cultured in vitro. Cell viability was detected by cell counting kit-8 (CCK-8) assay to find the optimal concentration of Na2S2O4. HT22 cells were divided into control group (NC group), OGD/R group (sugar-free medium+10 mmol/L Na2S2O4 treated for 90 minutes and then changed to normal medium for 4 hours) and hydrogen-rich water treatment group (HW group, sugar-free medium+10 mmol/L Na2S2O4 treated for 90 minutes and then changed to medium containing hydrogen-rich water for 4 hours). The morphology of HT22 cells was observed by inverted microscopy; cell activity was detected by CCK-8 method; cell ultrastructure was observed by transmission electron microscopy; the expression of microtubule-associated protein 1 light chain 3 (LC3) and Beclin-1 was detected by immunofluorescence; the protein expression of LC3II/I and Beclin-1, markers of cellular autophagy, was detected by Western blotting.@*RESULTS@#Inverted microscopy showed that compared with the NC group, the OGD/R group had poor cell status, swollen cytosol, visible cell lysis fragments and significantly lower cell activity [(49.1±2.7)% vs. (100.0±9.7)%, P < 0.01]; compared with the OGD/R group, the HW group had improved cell status and remarkably higher cell activity [(63.3±1.8)% vs. (49.1±2.7)%, P < 0.01]. Transmission electron microscopy showed that the neuronal nuclear membrane of cells in the OGD/R group was lysed and a higher number of autophagic lysosomes were visible compared with the NC group; compared with the OGD/R group, the neuronal damage of cells in the HW group was reduced and the number of autophagic lysosomes was notably decreased. The results of immunofluorescence assay showed that the expressions of LC3 and Beclin-1 were outstandingly enhanced in the OGD/R group compared with the NC group, and the expressions of LC3 and Beclin-1 were markedly weakened in the HW group compared with the OGD/R group. Western blotting assay showed that the expressions were prominently higher in both LC3II/I and Beclin-1 in the OGD/R group compared with the NC group (LC3II/I: 1.44±0.05 vs. 0.37±0.03, Beclin-1/β-actin: 1.00±0.02 vs. 0.64±0.01, both P < 0.01); compared with the OGD/R group, the protein expression of both LC3II/I and Beclin-1 in the HW group cells were notably lower (LC3II/I: 0.54±0.02 vs. 1.44±0.05, Beclin-1/β-actin: 0.83±0.07 vs. 1.00±0.02, both P < 0.01).@*CONCLUSIONS@#Hydrogen-rich water has a significant protective effect on OGD/R-causing HT22 cell injury, and the mechanism may be related to the inhibition of autophagy.

Phosphorylated PKM2 regulates endothelium-dependent vasodilation in diabetes / 中南大学学报(医学版)

OBJECTIVES@#Endothelium-dependent vasodilation dysfunction is the pathological basis of diabetic macroangiopathy. The utilization and adaptation of endothelial cells to high glucose determine the functional status of endothelial cells. Glycolysis pathway is the major energy source for endothelial cells. Abnormal glycolysis plays an important role in endothelium-dependent vasodilation dysfunction induced by high glucose. Pyruvate kinase isozyme type M2 (PKM2) is one of key enzymes in glycolysis pathway, phosphorylation of PKM2 can reduce the activity of pyruvate kinase and affect the glycolysis process of glucose. TEPP-46 can stabilize PKM2 in its tetramer form, reducing its dimer formation and phosphorylation. Using TEPP-46 as a tool drug to inhibit PKM2 phosphorylation, this study aims to explore the impact and potential mechanism of phosphorylated PKM2 (p-PKM2) on endothelial dependent vasodilation function in high glucose, and to provide a theoretical basis for finding new intervention targets for diabetic macroangiopathy.@*METHODS@#The mice were divided into 3 groups: a wild-type (WT) group (a control group, C57BL/6 mice) and a db/db group (a diabetic group, db/db mice), which were treated with the sodium carboxymethyl cellulose solution (solvent) by gavage once a day, and a TEPP-46 group (a treatment group, db/db mice+TEPP-46), which was gavaged with TEPP-46 (30 mg/kg) and sodium carboxymethyl cellulose solution once a day. After 12 weeks of treatment, the levels of p-PKM2 and PKM2 protein in thoracic aortas, plasma nitric oxide (NO) level and endothelium-dependent vasodilation function of thoracic aortas were detected. High glucose (30 mmol/L) with or without TEPP-46 (10 μmol/L), mannitol incubating human umbilical vein endothelial cells (HUVECs) for 72 hours, respectively. The level of NO in supernatant, the content of NO in cells, and the levels of p-PKM2 and PKM2 protein were detected. Finally, the effect of TEPP-46 on endothelial nitric oxide synthase (eNOS) phosphorylation was detected at the cellular and animal levels.@*RESULTS@#Compared with the control group, the levels of p-PKM2 in thoracic aortas of the diabetic group increased (P<0.05). The responsiveness of thoracic aortas in the diabetic group to acetylcholine (ACh) was 47% lower than that in the control group (P<0.05), and that in TEPP-46 treatment group was 28% higher than that in the diabetic group (P<0.05), while there was no statistically significant difference in the responsiveness of thoracic aortas to sodium nitroprusside (SNP). Compared with the control group, the plasma NO level of mice decreased in the diabetic group, while compared with the diabetic group, the phosphorylation of PKM2 in thoracic aortas decreased and the plasma NO level increased in the TEPP-46 group (both P<0.05). High glucose instead of mannitol induced the increase of PKM2 phosphorylation in HUVECs and reduced the level of NO in supernatant (both P<0.05). HUVECs incubated with TEPP-46 and high glucose reversed the reduction of NO production and secretion induced by high glucose while inhibiting PKM2 phosphorylation (both P<0.05). At the cellular and animal levels, TEPP-46 reversed the decrease of eNOS (ser1177) phosphorylation induced by high glucose (both P<0.05).@*CONCLUSIONS@#p-PKM2 may be involved in the process of endothelium-dependent vasodilation dysfunction in Type 2 diabetes by inhibiting p-eNOS (ser1177)/NO pathway.

Ultrashort wave alleviates oxygen -glucose deprivation/reoxygenation injury via up -regulation of SPCA1 expression in N2a cells / 中南大学学报(医学版)

OBJECTIVES@#Application of ultrashort wave (USW) to rats with cerebral ischemia and reperfusion injury could inhibit the decrease of expression of secretory pathway Ca2+-ATPase 1 (SPCA1), an important participant in Golgi stress, reduce the damage of Golgi apparatus and the apoptosis of neuronal cells, thereby alleviating cerebral ischemia-reperfusion injury. This study aims to investigate the effect of USW on oxygen-glucose deprivation/reperfusion (OGD/R) injury and the expression of SPCA1 at the cellular level.@*METHODS@#N2a cells were randomly divided into a control (Con) group, an OGD/R group, and an USW group. The cells in the Con group were cultured without exposure to OGD. The cells in the OGD/R group were treated with OGD/R. The cells in the USW group were treated with USW after OGD/R. Cell morphology was observed under the inverted phase-contrast optical microscope, cell activity was detected by cell counting kit-8 (CCK-8), apoptosis was detected by flow cytometry, and SPCA1 expression was detected by Western blotting.@*RESULTS@#Most of the cells in the Con group showed spindle shape with a clear outline and good adhesion. In the OGD/R group, cells were wrinkled, with blurred outline, poor adhesion, and lots of suspended dead cells appeared; compared with the OGD/R group, the cell morphology and adherence were improved, with clearer outlines and fewer dead cells in the USW group. Compared with the Con group, the OGD/R group showed decreased cell activity, increased apoptotic rate, and down-regulating SPCA1 expression with significant differences (all P<0.001); compared with the OGD/R group, the USW group showed increased cell activity, decreased apoptotic rate, and up-regulating SPCA1 expression with significant differences (P<0.01 or P<0.001).@*CONCLUSIONS@#USW alleviates the injury of cellular OGD/R, and its protective effect may be related to its up-regulation of SPCA1 expression.

Terpinen-4-ol inhibits proliferation of VSMCs exposed to high glucose via regulating KLF4/NF-κB signaling pathway / 中国中药杂志

This study aimed to observe the effect of terpinen-4-ol(T4O) on the proliferation of vascular smooth muscle cells(VSMCs) exposed to high glucose(HG) and reveal the mechanism via the Krüppel-like factor 4(KLF4)/nuclear factor kappaB(NF-κB) signaling pathway. The VSMCs were first incubated with T4O for 2 h and then cultured with HG for 48 h to establish the model of inflammatory injury. The proliferation, cell cycle, and migration rate of VSMCs were examined by MTT method, flow cytometry, and wound healing assay, respectively. The content of inflammatory cytokines including interleukin(IL)-6 and tumor necrosis factor-alpha(TNF-α) in the supernatant of VSMCs was measured by enzyme-linked immunosorbent assay(ELISA). Western blot was employed to determine the protein levels of proliferating cell nuclear antigen(PCNA), Cyclin D1, KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. The KLF4 expression in VSMCs was silenced by the siRNA technology, and then the effects of T4O on the cell cycle and protein expression of the HG-induced VSMCs were observed. The results showed that different doses of T4O inhibited the HG-induced proliferation and migration of VSMCs, increased the percentage of cells in G_1 phase, and decreased the percentage of cells in S phase, and down-regulated the protein levels of PCNA and Cyclin D1. In addition, T4O reduced the HG-induced secretion and release of the inflammatory cytokines IL-6 and TNF-α and down-regulated the expression of KLF4, NF-κB p-p65/NF-κB p65, IL-1β, and IL-18. Compared with si-NC+HG, siKLF4+HG increased the percentage of cells in G_1 phase, decreased the percentage of cells in S phase, down-regulated the expression of PCNA, Cyclin D1, and KLF4, and inhibited the activation of NF-κB signaling pathway. Notably, the combination of silencing KLF4 with T4O treatment further promoted the changes in the above indicators. The results indicate that T4O may inhibit the HG-induced proliferation and migration of VSMCs by down-regulating the level of KLF4 and inhibiting the activation of NF-κB signaling pathway.

Mitophagy mediated by ligustilide relieves OGD/R-induced injury in HT22 cells / 中国中药杂志

Mitochondrion, as the main energy-supply organelle, is the key target region that determines neuronal survival and death during ischemia. When an ischemic stroke occurs, timely removal of damaged mitochondria is very important for improving mitochondrial function and repairing nerve damage. This study investigated the effect of ligustilide(LIG), an active ingredient of Chinese medicine, on mitochondrial function and mitophagy based on the oxygen and glucose deprivation/reperfusion(OGD/R)-induced injury model in HT22 cells. By OGD/R-induced injury model was induced in vitro, HT22 cells were pre-treated with LIG for 3 h, and the cell viability was detected by the CCK-8 assay. Immunofluorescence and flow cytometry were used to detect indicators related to mitochondrial function, such as mitochondrial membrane potential, calcium overload, and reactive oxygen species(ROS). Western blot was used to detect the expression of dynamin-related protein 1(Drp1, mitochondrial fission protein) and cleaved caspase-3(apoptotic protein). Immunofluorescence was used to observe the co-localization of the translocase of outer mitochondrial membrane 20(TOMM20, mitochondrial marker) and lysosome-associated membrane protein 2(LAMP2, autophagy marker). The results showed that LIG increased the cell viability of HT22 cells as compared with the conditions in the model group. Furthermore, LIG also inhibited the ROS release, calcium overload, and the decrease in mitochondrial membrane potential in HT22 cells after OGD/R-induced injury, facilitated Drp1 expression, and promoted the co-localization of TOMM20 and LAMP2. The findings indicate that LIG can improve the mitochondrial function after OGD/R-induced injury and promote mitophagy. When mitophagy inhibitor mdivi-1 was administered, the expression of apoptotic protein increased, suggesting that the neuroprotective effect of LIG may be related to the promotion of mitophagy.

Progress in the role of endometrial glucose metabolism in embryo implantation / 生理学报

The synthesis and decomposition of glycogen adjust the blood glucose dynamically to maintain the energy supply required by the cells. As the only hormone that lowers blood sugar in the body, insulin can promote glycogen synthesis by activating the phosphatidylinositol 3-kinase (PI3K)/protein kinase B (Akt) signaling pathway and increasing glucose transporter translocation, and inhibit gluconeogenesis to lower blood glucose. In the endometrium, glycogen metabolism is active, but gluconeogenesis does not occur. The glycogen metabolism in the endometrium is controlled not only by the classical glucose regulating hormones, but also by the ovarian hormones. The functional activities related to implantation of the endometrium during the implantation window require glucose as energy source. A large amount of glucose is used to synthesize glycogen in the endometrium before implantation, which could meet the increased energy demand for embryo implantation. In diabetes, glycogen metabolism in the endometrium is impaired, which frequently leads to implantation failure and early abortion. This article reviews the glycogen metabolism in the endometrium and discusses its role in embryo implantation, which provide new ideas for embryo implantation research and infertility treatment.

Effect of açai supplementation (Euterpe Oleracea Mart) associated with exercise in animals and human: a scoping review / Efeitos da suplementação com açaí (Euterpe Oleracea Mart) associada ao exercício físico em animais e humanos: revisão de escopo

ABSTRACT Objective This scoping review aimed to map evidence on açai supplementation combined with exercise in animal and/or human experimental studies. Methods The search considered six electronic databases and screening of relevant references. The selection process and data extraction were performed by two independent authors. The study characteristics, and AS (e.g., form, intervention time, amount ingested) and exercise (e.g., types, intensity, and duration) strategies were summarized, as well as their reported results. Results From an initial total of 342 studies identified; 11 (5 with animal and 6 with human models) were eligible. In animals, açai supplementation and exercise led to benefits in exercise tolerance and improvements in several hemodynamic parameters, as well as significant improvements in liver markers and glucose metabolism. In humans, açai supplementation indicated positive results in increasing exhaustion time to 90% of VO2max and increasing intensity at the anaerobic threshold. Conclusion We conclude that future research involving animals and humans should examine açai supplementation and exercise with (a) obesity models to test the effect of adiponectin on body composition with analysis of histological and histochemical parameters; (b) eccentric injury protocols with the incorporation of muscle quality variables to assess recovery; (c) chronic açai supplementation and strength training; (d) comparison of different forms of açai supplementation in exercise protocols.

RESUMO Objetivo Esta revisão de escopo teve como objetivo mapear evidências sobre a suplementação com açaí combinada com exercícios físicos em estudos experimentais em animais e / ou humanos. Métodos A busca considerou seis bases de dados eletrônicas além da triagem de referências relevantes. O processo de seleção e extração de dados foi realizado por dois autores independentes. As características do estudo, estratégias de suplementação de açaí (forma, tempo de intervenção, e quantidade ingerida) e exercícios (tipos, intensidade e duração), seus resultados foram resumidos. Resultados Um total de 342 estudos foram inicialmente alcançados e somente 11 foram elegíveis (5 com animais e 6 com humanos). Em animais, a suplementação de açaí e os exercícios indicaram benefícios na tolerância ao exercício e melhorias em vários parâmetros hemodinâmicos, bem como melhorias significativas nos marcadores hepáticos e no metabolismo da glicose. Em humanos, a suplementação de açaí indicou resultados positivos no aumento do tempo de exaustão para 90% do VO2máx e no aumento da intensidade correspondente ao limiar anaeróbio. Conclusão Concluiu-se que pesquisas futuras envolvendo animais e humanos devem examinar a suplementação de açaí e exercícios com (a) modelos de obesidade para testar o efeito da adiponectina na composição corporal por meio de parâmetros histológicos e histoquímicos (b) protocolos de dano muscular excêntrico com incorporação de variáveis de qualidade muscular para avaliação da recuperação; (c) suplementação crônica de açaí e treinamento de força; (d) comparação das diferentes formas de suplementação de açaí em protocolos de exercícios.

Testosterone activates glucose metabolism through AMPK and androgen signaling in cardiomyocyte hypertrophy

BACKGROUND: Testosterone regulates nutrient and energy balance to maintain protein synthesis and metabolism in cardiomyocytes, but supraphysiological concentrations induce cardiac hypertrophy. Previously, we determined that testosterone increased glucose uptake­via AMP-activated protein kinase (AMPK)­after acute treatment in cardiomyocytes. However, whether elevated glucose uptake is involved in long-term changes of glucose metabolism or is required during cardiomyocyte growth remained unknown. In this study, we hypothesized that glucose uptake and glycolysis increase in testosterone-treated cardiomyocytes through AMPK and androgen receptor (AR). METHODS: Cultured cardiomyocytes were stimulated with 100 nM testosterone for 24 h, and hypertrophy was verified by increased cell size and mRNA levels of ß-myosin heavy chain (ß-mhc). Glucose uptake was assessed by 2-NBDG. Glycolysis and glycolytic capacity were determined by measuring extracellular acidification rate (ECAR). RESULTS: Testosterone induced cardiomyocyte hypertrophy that was accompanied by increased glucose uptake, glycolysis enhancement and upregulated mRNA expression of hexokinase 2. In addition, testosterone increased AMPK phosphorylation (Thr172), while inhibition of both AMPK and AR blocked glycolysis and cardiomyocyte hypertrophy induced by testosterone. Moreover, testosterone supplementation in adult male rats by 5 weeks induced cardiac hypertrophy and upregulated ß-mhc, Hk2 and Pfk2 mRNA levels. CONCLUSION: These results indicate that testosterone stimulates glucose metabolism by activation of AMPK and AR signaling which are critical to induce cardiomyocyte hypertrophy.

lncRNA in hepatic glucose and lipid metabolism: a review / 生物工程学报

In recent years, long non-coding RNA (lncRNA) has been proved to be involved in the regulation of biological processes at various levels, attracting research interests in life science. LncRNA possesses the unique capability and exert discrete effects on transcription, translation and post-translational modification of the target genes through interacting with DNA, RNA and protein. Current studies have revealed that lncRNA plays an important role in hepatic metabolism via diverse pathways. This review focuses on the function of lncRNA and its relationship with hepatic energy metabolism and the correlated diseases, to elucidate the underlying mechanisms and prospects of lncRNA researches.

Molecular mechanism of geniposide in regulating GLUT2 glycosylation in pancreatic β cells / 中国中药杂志

Type 2 diabetes mellitus( T2 DM) is a common chronic metabolic disease characterized by persistent hyperglycemia and insulin resistance. In pancreatic β-cells,glucose-stimulated insulin secretion( GSIS) plays a pivotal role in maintaining the balance of blood glucose level. Previous studies have shown that geniposide,one of the active components of Gardenia jasminoides,could quickly regulate the absorption and metabolism of glucose,and affect glucose-stimulated insulin secretion in pancreatic β cells,but the specific mechanism needs to be further explored. Emerging evidence indicated that glycosylation of glucose transporter( GLUT) has played a key role in sensing cell microenvironmental changes and regulating glucose homeostasis in eucaryotic cells. In this study,we studied the effects of geniposide on the key molecules of GLUT2 glycosylation in pancreatic β cells. The results showed that geniposide could significantly up-regulate the mRNA and protein levels of Glc NAc T-Ⅳa glycosyltransferase( Gn T-Ⅳa) and galectin-9 but had no signi-ficant effect on the expression of clathrin,and geniposide could distinctively regulate the protein level of Gn T-Ⅳa in a short time( 1 h) under the conditions of low and medium glucose concentrations,but had no significant effect on the protein level of galectin-9. In addition,geniposide could also remarkably affect the protein level of glycosylated GLUT2 in a short-time treatment. The above results suggested that geniposide could quickly regulate the protein level of Gn T-Ⅳa,a key molecule of protein glycosylation in INS-1 rat pancreatic βcells and affect the glycosylation of GLUT2. These findings suggested that the regulation of geniposide on glucose absorption,metabolism and glucose-stimulated insulin secretion might be associated with its efficacy in regulating GLUT2 glycosylation and affecting its distribution on the cell membrane and cytoplasm in pancreatic β cells.

Arachidonic acid metabolism in liver glucose and lipid homeostasis / 生理学报

Arachidonic acid (AA) is an ω-6 polyunsaturated fatty acid, which mainly exists in the cell membrane in the form of phospholipid. Three major enzymatic pathways including the cyclooxygenase (COX), lipoxygenase (LOX) and cytochrome P450 monooxygenase (CYP450) pathways are involved in AA metabolism leading to the generation of a variety of lipid mediators such as prostaglandins, leukotrienes, hydroxyeicosatetraenoic acids (HETEs) and epoxyeicoastrienoic acids (EETs). These bioactive AA metabolites play an important role in the regulation of many physiological processes including the maintenance of liver glucose and lipid homeostasis. As the central metabolic organ, the liver is essential in metabolism of carbohydrates, lipids and proteins, and its dysfunction is associated with the pathogenesis of many metabolic diseases such as type 2 diabetes mellitus, dyslipidemia and nonalcoholic fatty liver disease (NAFLD). This article aims to provide an overview of the enzymatic pathways of AA and discuss the role of AA-derived lipid mediators in the regulation of hepatic glucose and lipid metabolism and their associations with the pathogenesis of major metabolic disorders.

Effect of high-fat diet for rats at different stages on glucose and lipid metabolism in offspring and related mechanisms / 中国当代儿科杂志

OBJECTIVES@#To study the effect of high-fat diet for maternal Sprague-Dawley rats at different stages on glucose and lipid metabolism in offspring and related mechanisms.@*METHODS@#According to the diet before pregnancy and during pregnancy and lactation, maternal rats were randomly divided into four groups (@*RESULTS@#Compared with the control diet groups (CC and CH groups), the groups with high-fat diet before pregnancy (HC and HH groups) had a significant increase in body weight (@*CONCLUSIONS@#High-fat diet for rats at different stages before and after pregnancy has different effects on glucose and lipid metabolism of offspring rats, and high-fat diet before pregnancy and during pregnancy and lactation has the greatest effect. The effect of high-fat diet on glucose and lipid metabolism of offspring rats is considered associated with the changes in the expression of genes involved in glucose and lipid metabolism.

Deletion of CD36 gene ameliorates glucose metabolism abnormality induced by high-fat diet and promotes liver lipid accumulation / 生理学报

This study aimed to investigate the effects and the underlying mechanism of CD36 gene on glucose and lipid metabolism disorder induced by high-fat diet in mice. Wild type (WT) mice and systemic CD36 knockout (CD36

Developmental trend analysis and perspectives on researches related to hepatic glucose and lipid metabolism / 生理学报

The balance of glucose and lipid metabolism is a coordinated result of multiple factors and organs, and is one of the fundamental requirements for the maintenance of human health. As the most important organ for human metabolism, liver plays a key role in regulating glucose and lipid metabolism. With the advances of researches, the number of publications related to hepatic glucose and lipid metabolism has increased rapidly, which posed a challenge for grasping the hot research topics and developmental trends of hepatic glucose and lipid metabolism in a short time. To solve such problem, we developed an information analysis method, which systematically analyzes the research status, research techniques, and hot research topics of the hepatic glucose and lipid metabolism research field through Medical Subject Headings (MeSH) of related papers and high-throughput experimental data. The results showed that the number of publications related to hepatic glucose and lipid metabolism, especially publications by Chinese scholars, has increased dramatically in this century, along with the remarkable increment of the numbers of authors and affiliations per paper. Such increment is in part positively correlated with the impact of publications. Nowadays, various types of high-throughput experimental techniques have become the main research methods for genetic studies of hepatic glucose and lipid metabolism. Transcription factors, such as peroxisome proliferator-activated receptors (PPARs), sterol regulatory element binding proteins (SREBPs), and NF-E2-related factor 2 (Nrf2), have become the new research hotspots. These results systematically showed the current focuses and developmental trends of hepatic glucose and lipid metabolism research, and the data analysis method developed in this work can also be applied to other research fields.

The role and mechanism of amino acids in regulating hepatic glucose and lipid metabolism / 生理学报

Amino acids are essential nutrients for humans and have a wide range of biological functions. They are the constituent units of protein and energy metabolites. In addition, they are also widely involved in the maintenance and regulation of various physiological functions, and play a role in transcription, translation, post-translational modification and other levels. The liver is a key metabolic organ, and it acts as a hub that connects the metabolism of various tissues. Amino acid sensing plays a very important role in the regulation of hepatic glucose and lipid metabolism. Therefore, accurately sensing the levels of intracellular and extracellular amino acids is the key to maintaining cell homeostasis. There are several well-known amino acid sensors in eukaryotic cells, such as general control non-derepressible-2 (GCN2), mammalian target of rapamycin (mTOR) and taste receptors, which play an important role in maintaining metabolic homeostasis. This article gives a detailed introduction to the role and mechanism of amino acids in regulating hepatic glucose and lipid metabolism, laying a foundation for further exploration of amino acid sensing mechanism and treatment of hepatic glucose and lipid metabolism disorders.

Multimodal HIIT is more efficient than moderate continuous training for management of body composition, lipid profile and glucose metabolism in the diabetic elderly / El entrenamiento multimodal es más eficiente que el entrenamiento continuo moderado para el manejo de la composición corporal, el perfil de lípidos y el metabolismo de la glucosa en adultos mayores diabéticos

The exercise could play a central role to the fat management and glucose metabolism what can be a critical role in the health status of diabetic people, but the high intense exercise remains with controversial data about their effects. To identify the effect of the multimodal high-intensity interval training on body composition, lipid profile, and glucose metabolism in elderly diabetics. Methods: Elderly diabetic individuals (n = 48) were randomly divided in a Sedentary Control (SC) group, a Moderate-Intensity Continuous Training (MICT) group, and a High-Intensity Interval Training (HIIT) group. MICT and HITT were conducted over 60 days, 3x per week, with 40 minutes of exercise. Blood was collected prior to intervention, at four, and at eight weeks subsequently to assess glucose metabolism and lipid profiles. Body composition was determined before and after the intervention period. To verify the normality Kolmogorov-Smirnov statistical test was performed, followed by student "t" test or two-way ANOVA with Bonferroni's post hoc test with significance of 5 % the Cohen's f test to indicate the magnitude of the differences. HIIT significantly lowered cholesterol and triglyceride levels, and significantly lowered blood glucose and glycosylated haemoglobin levels (p<0.05). MICT and HIIT significantly increased levels of high-density lipoprotein, decreased total body mass and body mass index. HIIT resulted in significantly smaller waist circumferences, waist-to-hip ratios, and weight-to-height ratios over 60 days of training. HIIT is more effective than MICT for improving lipid and glycaemic profiles, decreasing body fat, and improving fat distribution elderly diabetics.

El ejercicio podría desempeñar un papel central en el manejo de la grasa y el metabolismo de la glucosa, lo que puede ser un papel crítico en el estado de salud de las personas diabéticas, pero el ejercicio intenso intenso sigue teniendo datos controvertidos sobre sus efectos. El objetivo del estudio fue identificar el efecto del entrenamiento multimodal de intervalos de alta intensidad sobre la composición corporal, el perfil lipídico y el metabolismo de la glucosa en diabéticos de edad avanzada. Los individuos diabéticos de edad avanzada (n = 48) se dividieron aleatoriamente en un grupo de control sedentario (SC), un grupo de entrenamiento continuo de intensidad moderada (MICT) y un grupo de entrenamiento de intervalos de alta intensidad (HIIT). MICT y HITT se realizaron durante 60 días, 3 veces por semana, con 40 minutos de ejercicio. Se recogió sangre antes de la intervención, a las cuatro y a las ocho semanas posteriormente para evaluar el metabolismo de la glucosa y los perfiles de lípidos. La composición corporal se determinó antes y después del período de intervención. Para verificar la normalidad se realizó la prueba estadística de Kolmogorov-Smirnov, seguida de la prueba "t" de Student o ANOVA de dos vías con la prueba post hoc de Bonferroni con una significancia del 5 % de la prueba f de Cohen, indicando las diferencias. HIIT redujo significativamente los niveles de colesterol y triglicéridos, además de reducir de manera importante los niveles de glucosa en la sangre y la hemoglobina glicosilada (p <0.05). MICT y HIIT aumentaron significativamente los niveles de lipoproteína de alta densidad, disminuyeron la masa corporal total y el índice de masa corporal. HIIT resultó en circunferencias de cintura significativamente más pequeñas, relaciones cintura-cadera y relaciones peso-altura durante 60 días de entrenamiento. HIIT es más efectivo que MICT para mejorar los perfiles de lípidos y glucémicos, disminuir la grasa corporal y mejorar la distribución de grasa en los diabéticos de edad avanzada.

SGLT-2 inhibitors in diabetes: a focus on renoprotection

SUMMARY Type 2 diabetes mellitus is an important public health problem, with a significant impact on cardiovascular morbidity and mortality and an important risk factor for chronic kidney disease. Various hypoglycemic therapies have proved to be beneficial to clinical outcomes, while others have failed to provide an improvement in cardiovascular and renal failure, only reducing blood glucose levels. Recently, sodium-glucose cotransporter-2 (SGLT2) inhibitors, represented by the empagliflozin, dapagliflozin, and canagliflozin, have been showing satisfactory and strong results in several clinical trials, especially regarding the reduction of cardiovascular mortality, reduction of hospitalization due to heart failure, reduction of albuminuria, and long-term maintenance of the glomerular filtration rate. The benefit from SGLT2 inhibitors stems from its main mechanism of action, which occurs in the proximal tubule of the nephron, causing glycosuria, and a consequent increase in natriuresis. This leads to increased sodium intake by the juxtaglomerular apparatus, activating the tubule glomerular-feedback and, finally, reducing intraglomerular hypertension, a frequent physiopathological condition in kidney disease caused by diabetes. In addition, this class of medication presents an appropriate safety profile, and its most frequently reported complication is an increase in the incidence of genital infections. Thus, these hypoglycemic agents gained space in practical recommendations for the management of type 2 diabetes mellitus and should be part of the initial therapeutic approach to provide, in addition to glycemic control, cardiovascular outcomes, and the renoprotection in the long term.