Correction: Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice.
Ontology highlight
ABSTRACT:
SUBMITTER: Handa K
PROVIDER: S-EPMC4868301 | biostudies-other | 2016
REPOSITORIES: biostudies-other
Publications
Correction: Long-Term Low Carbohydrate Diet Leads to Deleterious Metabolic Manifestations in Diabetic Mice.
Handa Keiko K Inukai Kouichi K Onuma Hirohisa H Kudo Akihiko A Nakagawa Fumiyuki F Tsugawa Kazue K Kitahara Atsuko A Moriya Rie R Takahashi Kazuto K Sumitani Yoshikazu Y Hosaka Toshio T Kawakami Hayato H Oyadomari Seiichi S Ishida Hitoshi H
PloS one 20160516 5
[This corrects the article DOI: 10.1371/journal.pone.0104948.]. ...[more]
Similar Datasets
Project description:Obesity and metabolic syndrome are of increasing global concern. In order to understand the basic biology and etiology of obesity, research has turned to animals across the vertebrate spectrum including zebrafish. Here, we carefully characterize zebrafish in a long-term obesogenic environment as well as zebrafish that went through early lifetime caloric restriction. We found that long-term obesity in zebrafish leads to metabolic endpoints comparable to mammals including increased adiposity, weight, hepatic steatosis and hepatic lesions but not signs of glucose dysregulation or differences in metabolic rate or mitochondrial function. Malnutrition in early life has been linked to an increased likelihood to develop and an exacerbation of metabolic syndrome, however fish that were calorically restricted from five days after fertilization until three to nine months of age did not show signs of an exacerbated phenotype. In contrast, the groups that were shifted later in life from caloric restriction to the obesogenic environment did not completely catch up to the long-term obesity group by the end of our experiment. This dataset provides insight into a slowly exacerbating time-course of obesity phenotypes.
| S-EPMC9094543 | biostudies-literature
Project description:Metabolic syndrome can induce chronic kidney disease in humans. Genetically engineered mice on a C57BL/6 background are highly used for mechanistic studies. Although it has been shown that metabolic syndrome induces cardiovascular lesions in C57BL/6 mice, in depth renal phenotyping has never been performed. Therefore in this study we characterized renal function and injury in C57BL/6 mice with long-term metabolic syndrome induced by a high fat and fructose diet (HFFD). C57BL/6 mice received an 8 months HFFD diet enriched with fat (45% energy from fat) and drinking water enriched with fructose (30%). Body weight, food/water consumption, energy intake, fat/lean mass ratio, plasma glucose, HDL, LDL, triglycerides and cholesterol levels were monitored. At 3, 6 and 8 months, renal function was determined by inulin clearance and measure of albuminuria. At sacrifice, kidneys and liver were collected. Metabolic syndrome in C57BL/6 mice fed a HFFD was observed as early 4 weeks with development of type 2 diabetes at 8 weeks after initiation of diet. However, detailed analysis of kidney structure and function showed only minimal renal injury after 8 months of HFFD. HFFD induced moderate glomerular hyperfiltration (436,4 µL/min vs 289,8 µL/min; p-value=0.0418) together with a 2-fold increase in albuminuria only after 8 months of HFFD. This was accompanied by a 2-fold increase in renal inflammation (p-value=0.0217) but without renal fibrosis or mesangial matrix expansion. In addition, electron microscopy did not show alterations in glomeruli such as basal membrane thickening and foot process effacement. Finally, comparison of the urinary peptidome of these mice with the urinary peptidome from humans with diabetic nephropathy also suggested absence of diabetic nephropathy in this model. This study provides evidence that the HFFD C57BL/6 model is not the optimal model to study the effects of metabolic syndrome on the development of diabetic kidney disease.
| S-EPMC3789664 | biostudies-literature
Project description:Phenylketonuria (PKU) is an inherited metabolic disorder caused by mutation within phenylalanine hydroxylase (PAH) gene. Loss-of-function of PAH leads to accumulation of phenylalanine in the blood/body of an untreated patient, which damages the developing brain, causing severe mental retardation. Current gene therapy strategies based on adeno-associated vector (AAV) delivery of PAH gene were effective in male animals but had little long-term effects on blood hyperphenylalaninemia in females. Here, we designed a gene therapy strategy using AAV to deliver a human codon-optimized phenylalanine amino lyase in a liver-specific manner. It was shown that PAL was active in lysing phenylalanine when it was expressed in mammalian cells. We produced a recombinant adeno-associated vector serotype 8 (AAV8) viral vector expressing the humanized PAL under the control of human antitrypsin (hAAT) promoter (AAV8-PAL). A single intravenous administration of AAV8-PAL caused long-term correction of hyperphenylalaninemia in both male and female PKU mice (strain Pahenu2). Besides, no obvious liver injury was observed throughout the treatment process. Thus, our results established that AAV-mediated liver delivery of PAL gene is a promising strategy in the treatment of PKU.
| S-EPMC7733040 | biostudies-literature
Project description:UnlabelledBackgroundReduction of dietary carbohydrates and corresponding insulin doses stabilizes and lowers mean blood glucose in individuals with type 1 diabetes within days. The long-term adherence for persons who have learned this technique is unknown. To assess adherence over 4?years in such a group the present audit was done retrospectively by record analysis for individuals who have attended an educational course. Adherence was assessed from HbA1c changes and individuals' own reports.FindingsAltogether 48 persons with diabetes duration of 24?±?12?years and HbA1c?>?= 6.1% (Mono-S; DCCT?=?7.1%) attended the course. Mean HbA1c for all attendees was at start, at 3?months and 4?years 7.6%?±?1.0%, 6.3?±?0.7%, 6.9?±?1.0% respectively. The number of non-adherent persons was 25 (52%). HbA1c in this group was at start, at 3?months and 4?years: 7.5 ±1.1%, 6.5?±?0.8%, 7.4?±?0.9%. In the group of 23 (48%) adherent persons mean HbA1c was at start, at 3?months and 4?years 7.7?±?1.0%, 6.4?±?0.9%, 6.4?±?0.8%.ConclusionAttending an educational course on dietary carbohydrate reduction and corresponding insulin reduction in type 1 diabetes gave lasting improvement. About half of the individuals adhered to the program after 4?years. The method may be useful in informed and motivated persons with type 1 diabetes. The number needed to treat to have lasting effect in 1 was 2.
| S-EPMC3583262 | biostudies-literature
Project description:Gene therapy for beta-thalassemia requires stable transfer of a beta-globin gene into hematopoietic stem cells (HSCs) and high and regulated hemoglobin expression in the erythroblastic progeny. We developed an erythroid-specific lentiviral vector driving the expression of the human beta-globin gene from a minimal promoter/enhancer element containing two hypersensitive sites from the beta-globin locus control region. Transplantation of transduced HSCs into thalassemic mice leads to stable and long-term correction of anemia with all red blood cells expressing the transgene. A frequency of 30-50% of transduced HSCs, harboring an average vector copy number per cell of 1, was sufficient to fully correct the thalassemic phenotype. In the mouse model of Cooley's anemia transplantation of transduced cells rescues lethality, leading to either a normal or a thalassemia intermedia phenotype. We show that genetically corrected erythroblasts undergo in vivo selection with preferential survival of progenitors harboring proviral integrations in genome sites more favorable to high levels of vector-derived expression. These data provide a rationale for a gene therapy approach to beta-thalassemia based on partially myeloablative transplantation protocols.
| S-EPMC2492493 | biostudies-other
Project description:To understand what determines the success of short- and long-term weight loss, we conduct a secondary analysis of dietary, metabolic, and molecular data collected from 609 participants before, during, and after a 1-year weight-loss intervention with either a healthy low-carbohydrate (HLC) or a healthy low-fat (HLF) diet. Through systematic analysis of multidomain datasets, we find that dietary adherence and diet quality, not just caloric restriction, are important for short-term weight loss in both diets. Interestingly, we observe minimal dietary differences between those who succeeded in long-term weight loss and those who did not. Instead, proteomic and gut microbiota signatures significantly differ between these two groups at baseline. Moreover, the baseline respiratory quotient may suggest a specific diet for better weight-loss outcomes. Overall, the identification of these dietary, molecular, and metabolic factors, common or unique to the HLC and HLF diets, provides a roadmap for developing individualized weight-loss strategies.
| S-EPMC9798029 | biostudies-literature
Project description:A decrease in TCA cycle activity may lead to impaired nutrition metabolism and cellular energy shortage. Herein, we aimed to characterize the detailed metabolic changes that compensate for energy shortages in energy-consuming organs (heart and skeletal muscles) in mice with knockout of citrate synthase (CS), an important enzyme in the TCA cycle. CS hetero knockout (CS +/-) mice and wild-type mice were fed a low-carbohydrate ketogenic diet (LCKD) or high-fat, high-carbohydrate diet (HFHCD) to induce metabolic changes. Body weight, blood serum parameters, metabolic gene expression, and adenosine triphosphate (ATP) levels were measured in the heart and skeletal muscles. Glycogen content, anabolic and catabolic biomarkers, and morphological changes were also assessed in the skeletal muscles. After diet feeding, there were no differences observed in the body weight and blood serum parameters between wild-type and CS +/- mice. The cardiac expression of genes related to the utilization of fatty acids, monocarboxylates, and branched amino acids increased in LCKD-fed CS +/- mice. In contrast, no significant differences in gene expression were observed in the muscles of LCKD-fed mice or the heart and muscles of HFHCD-fed mice. ATP levels decreased only in the skeletal muscles of LCKD-fed CS +/- mice. Additionally, the decrease in glycogen content, suppression of p70 S6 kinase, and presence of type I fiber atrophy were observed in the muscles of LCKD-fed CS +/- mice. These results suggest that the energy-consuming organs with CS insufficiency may undergo tissue-specific adaption to compensate for energy shortages when the carbohydrate supply is limited.
| S-EPMC9302927 | biostudies-literature
Project description:Low-carbohydrate diets are used to manage obesity, seizure disorders, and malignancies of the central nervous system. These diets create a distinctive, but incompletely defined, cellular, molecular, and integrated metabolic state. Here, we determine the systemic and hepatic effects of long-term administration of a very low-carbohydrate, low-protein, and high-fat ketogenic diet, serially comparing these effects to a high-simple-carbohydrate, high-fat Western diet and a low-fat, polysaccharide-rich control chow diet in C57BL/6J mice. Longitudinal measurement of body composition, serum metabolites, and intrahepatic fat content, using in vivo magnetic resonance spectroscopy, reveals that mice fed the ketogenic diet over 12 wk remain lean, euglycemic, and hypoinsulinemic but accumulate hepatic lipid in a temporal pattern very distinct from animals fed the Western diet. Ketogenic diet-fed mice ultimately develop systemic glucose intolerance, hepatic endoplasmic reticulum stress, steatosis, cellular injury, and macrophage accumulation, but surprisingly insulin-induced hepatic Akt phosphorylation and whole-body insulin responsiveness are not impaired. Moreover, whereas hepatic Pparg mRNA abundance is augmented by both high-fat diets, each diet confers splice variant specificity. The distinctive nutrient milieu created by long-term administration of this low-carbohydrate, low-protein ketogenic diet in mice evokes unique signatures of nonalcoholic fatty liver disease and whole-body glucose homeostasis.
| S-EPMC3119109 | biostudies-literature
Project description:The nuclear factor E2-related factor 2 (Nrf2)-Kelch-like ECH-associated protein 1 (Keap1) pathway upregulates antioxidant and biotransformation enzyme expression to counter cellular oxidative stress. The contributions of Nrf2 to other cellular functions, such as lipid homeostasis, are emerging. This study was conducted to determine how enhanced Nrf2 activity influences the progression of metabolic syndrome with long-term high-fat diet (HFD) feeding. C57BL/6 and Keap1-knockdown (Keap1-KD) mice, which exhibit enhanced Nrf2 activity, were fed a HFD for 24 weeks. Keap1-KD mice had higher body weight and white adipose tissue mass compared to C57BL/6 mice on HFD, along with increased inflammation and lipogenic gene expression. HFD feeding increased hepatic steatosis and inflammation to a greater extent in Keap1-KD mice compared to C57BL/6 mice, which was associated with increased liver Cd36, fatty acid-binding protein 4, and monocyte chemoattractant protein 1 mRNA expression, as well as increased acetyl-CoA carboxylase 1 and stearoyl-CoA desaturase-1 protein expression. The HFD altered short-term glucose homeostasis to a greater degree in Keap-KD mice compared to C57BL/6 mice, which was accompanied by downregulation of insulin receptor substrate 1 mRNA expression in skeletal muscle. Together, the results indicate that Keap1 knockdown, on treatment with HFD, increases certain markers of metabolic syndrome.
| S-EPMC3797262 | biostudies-literature
Project description:Evidence is mounting that chronic high-fructose diets (HFrD) can lead to metabolic abnormalities and cause a variety of diseases. However, the underlying mechanism by which long-term high fructose intake influencing systemic metabolism remains unclarified. This study, therefore, attempted to investigate the impact of a high-fructose diet on metabolic profile. Four-week-old male C57BL/6 mice were fed with 15% fructose solution as their only source of water for 8 weeks. Afterward, gas chromatography-mass spectrometry (GC-MS) was employed to investigate the comprehensive metabolic profile of serum, muscle, liver, heart, white adipose, brain, and kidney tissues, and multivariate analyses including principal component analysis (PCA) and orthogonal partial least squared-discriminant analysis (OPLS-DA) were applied to screen for differential metabolite expression between the HFrD and control groups. Furthermore, the MetaboAnalyst 5.0 (http://www.metaboanalyst.ca) and Kyoto Encyclopedia of Genes and Genomes database (KEGG; http://www.kegg.jp) were employed to portray a detailed metabolic network. This study identified 62 metabolites related to HFrD and 10 disturbed metabolic pathways. The results indicated that high fructose intake mainly influenced amino acid metabolism and biosynthesis (glycine, serine, and threonine metabolism; aspartate, and glutamate metabolism; phenylalanine, tyrosine, and tryptophan biosynthesis, and arginine biosynthesis pathways), glutathione metabolism, sphingolipid metabolism, and glyoxylate and dicarboxylate metabolism in serum, whereas these pathways were suppressed in the brain. Starch and sucrose metabolism in muscle was also disrupted. These results elucidate the effects of long-term high fructose consumption on the metabolic profiles of various tissues and provide new insight for the identification of potential metabolic biomarkers and pathways disrupted by high fructose.
| S-EPMC9353457 | biostudies-literature