scholarly journals Vitamin A Status Regulates the Development of Obesity and Type 2 Diabetes in Zucker Diabetic Fatty Rats

2021 ◽  
Vol 5 (Supplement_2) ◽  
pp. 531-531
Author(s):  
Tiannan Wang ◽  
Guoxun Chen
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Fatty Acid Biosynthesis ◽  
The Body ◽  
Oral Glucose ◽  
Acid Biosynthesis ◽  
Expression Levels ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats

Abstract Objectives Here, we studied the effects of VA status on the development of obesity and type 2 diabetes in Zucker diabetic fat (ZDF) rats. Methods Zucker Lean (ZL) and ZDF rats at weaning were divided into 6 groups, VA deficient with basal fat (VAD-BF, 0 mg retinyl palmitate (RP)/kg and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg RP/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high-fat (VAD-HF, 60% fat energy), VAM-HF and VAS-HF diets, and fed for 8 weeks (w). The body mass (BM), and peripheral blood glucose (PBG) were measured weekly. An oral glucose tolerance test (OGTT) were done at 6.5 and 7.5w,  respectively. Plasma levels of glucose, insulin, triacylglycerol and cholesterol l were determined using commercially available kits. The expression levels of genes and proteins in the liver of rats were analyzed using PCR and Western blot. Results VAS-BF ZL and ZDF rats from 6w had respectively higher BM than VAD/VAM-BF ZL and ZDF rats. VAS-HF ZL and ZDF rats from 4w had respectively higher BM than VAD/VAM-HF ZL and ZDF rats. VAS-BF/HF ZDF rats from 6w had respectively higher PBG levels than VAD/VAM-BF/HF ZDF rats. The OGTT AUC values of VAS-BF/HF ZL/ZDF rats were respectively higher than that of VAD/VAM-BF/HF ZL/ZDF rats. The levels of glucose, insulin, triacylglycerol and cholesterol in VAD/VAM/VAS-BF ZDF and VAD/VAM/VAS-HF ZDF rats were higher than that in BF ZL rats (except for the glucose level) and HF ZL rats, respectively. The hepatic Gck mRNA and its protein levels in VAD-BF ZL rats were lower than that in VAS-BF ZL rats. The hepatic levels of Fas, and Acl mRNA and FAS, and ACL proteins in VAM/VAS-HF ZF rats were higher than that in VAM/VAS-HF ZL rats. The hepatic retinol content of VAD-BF/HF ZL/ZDF rats were lower than that of VAM groups, which are lower than that of VAS-BF/HF ZL/ZDF rats. Conclusions VA statuses affect BM gain in ZL and ZDF rats fed a BF or a HF diet. The expression levels of mRNAs and proteins in the fatty acid biosynthesis pathways were reduced in VAD-HF ZDF rats. The effects of VA on fatty acid biosynthesis in ZDF rats were masked in a HF diet setting. Reduced VA intake prevents obesity, and type 2 diabetes in ZDF rats. Funding Sources Diabetes Action Research and Education Foundation

scholarly journals Vitamin A Status Regulates the Development of Obesity and Type 2 Diabetes in Zucker Diabetic Fatty Rats

2020 ◽  
Vol 4 (Supplement_2) ◽  
pp. 672-672
Author(s):  
Tiannan Wang ◽  
Guoxun Chen
Keyword(s):  
Type 2 Diabetes ◽  
Vitamin A ◽  
Area Under The Curve ◽  
Tolerance Test ◽  
Retinyl Palmitate ◽  
The Body ◽  
Oral Glucose ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats

Abstract Objectives We have shown that vitamin A (VA) status regulates obesity and fuel metabolism in rats. Here, we studied the effects of VA status on the development of obesity and type 2 diabetes in Zucker diabetic fat (ZDF) rats. Methods Zucker Lean (ZL) and ZDF rats at weaning were divided into 6 groups, VA deficient with basal fat (VAD-BF, 0 mg retinyl palmitate (RP)/kg and 22.1% fat energy), VA marginal with BF (VAM-BF, 0.35 mg RP/kg), VA sufficient with BF (VAS-BF, 4.0 mg RP/kg), VAD with high-fat (VAD-HF, 60% fat energy), VAM-HF and VAS-HF diets, and fed for 8 weeks (w). The body mass (BM), and peripheral blood glucose (PBG) were measured weekly. Insulin tolerance test (ITT) and oral glucose tolerance test (OGTT) were done at 6.5 and 7.5 w, respectively. At the end of the feeding, blood, liver and white adipose tissue (WTA) samples were collected. Results VAS-BF ZL and ZDF rats from 6 w had respectively higher BM than VAD/VAM-BF ZL and ZDF rats. VAS-HF ZL and ZDF rats from 4 w had respectively higher BM than VAD/VAM-HF ZL and ZDF rats. The liver/BM and WAT/BM ratios in VAD/VAM-BF/HF ZL and ZDF V rats were respectively lower than that of VAS-BF/HF groups. VAS-BF/HF ZDF rats from 6 w had respectively higher PBG levels than VAD/VAM-BF/HF ZDF rats. In ITT, PBG levels of VAD/VAM/VAS-BF ZL rats dropped until 15 mins. PBG levels of VAD-HF and VAM/VAS-HF ZL rats declined until 30 mins and 15 mins, respectively. PBG levels of VAM-BF and VAS-BF ZDF rats dropped until 15 mins and 5 mins, respectively. PBG levels of VAD-BF ZDF rats start to dropped after 10 mins and stopped after 20 mins. PBG levels of VAD/VAM-HF and VAS-HF ZDF rats dropped until 15 mins and 20 mins, respectively. The OGTT results showed that PBG levels of VAS-BF ZL rats peaked at 10 mins, and VAS-BF/HF ZL rats had respectively higher PBG levels than VAD/VAM-BF/HF ZL rats. PBG levels of all ZDF rats peaked at 60 mins (except for VAS-BF ZDF rats at 30) before dropped. TheOGTT area under the curve values of VAS-BF/HF ZL or ZDF rats were respectively higher than that of VAD/VAM-BF/HF ZL or ZDF rats, and that of VAM-HF ZL rats were higher than that of VAD-HF ZL rats. Conclusions VA statuses affect BM gain in ZL and ZDF rats in BF and HF diets. Reduced VA intake prevents obesity, and type 2 diabetes in ZDF rats. Funding Sources Diabetes Action Research and Education Foundation.

scholarly journals Analysis of gene expression profiles in insulin-sensitive tissues from pre-diabetic and diabetic Zucker diabetic fatty rats

2005 ◽  
Vol 34 (2) ◽  
pp. 299-315 ◽  
Author(s):  
Young Ho Suh ◽  
Younyoung Kim ◽  
Jeong Hyun Bang ◽  
Kyoung Suk Choi ◽  
June Woo Lee ◽  
...  
Keyword(s):  
Gene Expression ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Expression Profiles ◽  
Gene Expression Profiles ◽  
Zucker Diabetic Fatty Rats ◽  
Zdf Rats

Insulin resistance occurs early in the disease process, preceding the development of type 2 diabetes. Therefore, the identification of molecules that contribute to insulin resistance and leading up to type 2 diabetes is important to elucidate the molecular pathogenesis of the disease. To this end, we characterized gene expression profiles from insulin-sensitive tissues, including adipose tissue, skeletal muscle, and liver tissue of Zucker diabetic fatty (ZDF) rats, a well characterized type 2 diabetes animal model. Gene expression profiles from ZDF rats at 6 weeks (pre-diabetes), 12 weeks (diabetes), and 20 weeks (late-stage diabetes) were compared with age- and sex-matched Zucker lean control (ZLC) rats using 5000 cDNA chips. Differentially regulated genes demonstrating > 1.3-fold change at age were identified and categorized through hierarchical clustering analysis. Our results showed that while expression of lipolytic genes was elevated in adipose tissue of diabetic ZDF rats at 12 weeks of age, expression of lipogenic genes was decreased in liver but increased in skeletal muscle of 12 week old diabetic ZDF rats. These results suggest that impairment of hepatic lipogenesis accompanied with the reduced lipogenesis of adipose tissue may contribute to development of diabetes in ZDF rats by increasing lipogenesis in skeletal muscle. Moreover, expression of antioxidant defense genes was decreased in the liver of 12-week old diabetic ZDF rats as well as in the adipose tissue of ZDF rats both at 6 and 12 weeks of age. Cytochrome P450 (CYP) genes were also significantly reduced in 12 week old diabetic liver of ZDF rats. Genes involved in glucose utilization were downregulated in skeletal muscle of diabetic ZDF rats, and the hepatic gluconeogenic gene was upregulated in diabetic ZDF rats. Genes commonly expressed in all three tissue types were also observed. These profilings might provide better fundamental understanding of insulin resistance and development of type 2 diabetes.

Antidiabetic properties of purified polysaccharide fromHedysarum polybotrys

2010 ◽  
Vol 88 (1) ◽  
pp. 64-72 ◽  
Author(s):  
Fangdi Hu ◽  
Xiaodong Li ◽  
Lianggong Zhao ◽  
Shilan Feng ◽  
Chunming Wang
Keyword(s):  
Nitric Oxide ◽  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Density Lipoprotein ◽  
Control Group ◽  
Hepatic Glycogen ◽  
Oral Glucose ◽  
Synthetase Activity ◽  
Molecular Weight Range

Hedysarum polybotrys polysaccharide (HPS) is the principal active fraction responsible for the antidiabetic properties of this species. The aim of this study was to determine the antidiabetic properties of 4 purified fractions of different molecular weight range HPSs (HPS1, HPS2, HPS3, HPS4). HPS3 was selected for examination of its hypoglycemic mechanism because of its significant hypoglycemic effect in alloxan-induced diabetic mice. The changes in blood glucose levels and oral glucose tolerance tests (OGTT) showed that hypoglycemia was more pronounced in HPS3-treated groups than in the diabetes mellitus model (DM) control group. The interleukin-6, tumor necrosis factor-α, leptin, and free fatty acid levels were significantly lower in the HPS3-treated groups and HPS3 + metformin (HPS3+MET) group than in the DM control group, while plasma insulin, hepatic glycogen, superoxide dismutase, and nitric oxide synthetase activity were significantly higher. Treatment with HPS3 or HPS3+MET also significantly lowered malonaldehyde levels compared with the DM control group, while it elevated the nitric oxide and total antioxidant capacity. HPS3 altered the plasma lipid levels by lowering cholesterol and triglyceride concentrations, while elevating the plasma high-density lipoprotein cholesterol level. Therefore, these results suggest that HPS3 may partly ameliorate hyperglycemia and hyperlipidemia associated with type 2 diabetes through increased insulin secretion, inhibition of lipid peroxidation, promotion of sensitivity to insulin, suppression of gluconeogenesis and reduction in the biosynthesis fatty acid, cholesterol and cell cytokines related to insulin resistance, and it could be a useful adjunct therapy to a proven first-line therapy for type 2 diabetes using metformin.

scholarly journals Characterization of Novel Nonobese Type 2 Diabetes Rat Model with Enlarged Kidneys

2019 ◽  
Vol 2019 ◽  
pp. 1-9 ◽  
Author(s):  
Ayaka Domon ◽  
Kentaro Katayama ◽  
Yuki Tochigi ◽  
Hiroetsu Suzuki
Keyword(s):  
Type 2 Diabetes ◽  
Rat Model ◽  
Inflammatory Cells ◽  
The Body ◽  
Female Rats ◽  
Male Rats ◽  
Oral Glucose ◽  
Renal Tubules ◽  
Age Related

A variety of animal models of diabetes mellitus (DM) are required to study the genetics and pathophysiology of DM. We established a novel rat strain showing nonobese type 2 diabetes with enlarged kidneys from the LEA.PET-pet congenic strain and named it Diabetes with Enlarged Kidney (DEK). The body growth of DEK affected rats was similar to that of normal rats before the development of DM but was attenuated with the deterioration of DM. There was a marked difference in the etiology of DEK by gender: DM phenotypes including polyuria, polydipsia, and hyperglycemia (nonfasting blood glucose over 300 mg/dl) were found in male rats aged over 10 weeks but not in female rats. The cumulative incidence of DM in DEK males at the age of 30 weeks was 44.8%. Oral glucose tolerance tests showed glucose intolerance and decreased insulin secretion in response to glucose loading in affected males, features which were exacerbated with age. Affected males exhibited disorganized architecture of pancreatic islets, decreased numbers of β cells, and markedly decreased expression of insulin, despite no pathological findings of hemorrhage or infiltration of inflammatory cells in the pancreatic islet. Age-related islet fibrosis appeared similar in normal and affected males. Affected males also showed enlarged kidneys with dilation of renal tubules in both the cortex and medulla, but no obvious glomerular lesions typical of diabetic nephropathy (DN) at the age of 30 weeks. Plasma levels of urea nitrogen and creatinine were normal, but hypoalbuminemia was detected. These pathophysiological features in affected males indicated that their renal function was almost maintained despite severe DM. Taken together, these findings indicate that the affected males of the DEK strain are a novel nonobese type 2 diabetes rat model useful for studying the mechanisms underlying β cell loss and identifying genetic factors protective against DN.

scholarly journals Down Regulation Of The Expression Of Mitochondrial Phosphopantetheinyl-Proteins In Pantothenate Kinase-Associated Neurodegeneration: Pathophysiological Consequences and Therapeutic Perspectives

2021 ◽  
Author(s):  
Mónica Álvarez-Córdoba ◽  
Marta Talaverón-Rey ◽  
Irene Villalón-García ◽  
Suleva Povea-Cabello ◽  
Juan M. Suárez-Rivero ◽  
...  
Keyword(s):  
Fatty Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
Iron Accumulation ◽  
Muscle Rigidity ◽  
Type I ◽  
Acid Biosynthesis ◽  
Pantothenate Kinase ◽  
Expression Levels ◽  
Positive Effects

Abstract BackgroundNeurodegeneration with brain iron accumulation (NBIA) is a group of genetic neurological disorders frequently associated with iron accumulation in the basal nuclei of the brain characterized by progressive spasticity, dystonia, muscle rigidity, neuropsychiatric symptoms, and retinal degeneration or optic nerve atrophy. Pantothenate kinase-associated neurodegeneration (PKAN) is the most widespread NBIA disorder. It is caused by mutations in the gene of pantothenate kinase 2 (PANK2) which catalyzes the first reaction of coenzyme A (CoA) biosynthesis. Thus, altered PANK2 activity is expected to induce CoA deficiency as well as low levels of essential metabolic intermediates such as 4′-phosphopantetheine which is a necessary cofactor for critical proteins involved in cytosolic and mitochondrial pathways such as fatty acid biosynthesis, mitochondrial respiratory complex I assembly and lysine and tetrahydrofolate metabolism, among other metabolic processes.MethodsIn this manuscript, we examined the effect of PANK2 mutations on the expression levels of proteins with phosphopantetheine cofactors in fibroblast derived from PKAN patients. These proteins include cytosolic acyl carrier protein (ACP), which is integrated within the multifunctional polypeptide chain of the fatty acid synthase involved in cytosolic fatty acid biosynthesis type I (FASI); mitochondrial ACP (mtACP) associated with mitocondrial fatty acid biosynthesis type II (FASII); mitochondrial alpha-aminoadipic semialdehyde synthase (AASS); and 10-formyltetrahydrofolate dehydrogenases (cytosolic, ALD1L1, and mitochondrial, ALD1L2). ResultsIn PKAN fibroblasts the expression levels of cytosolic FAS and ALD1L1 were not affected while the expression levels of mtACP, AASS and ALD1L2 were markedly reduced, suggesting that 4′-phosphopantetheinylation of mitochondrial but no cytosolic proteins were markedly affected in PKAN patients. Furthermore, the correction of PANK2 expression levels by treatment with pantothenate in selected mutations with residual enzyme content was able to correct the expression levels of mitochondrial phosphopantetheinyl-proteins and restore the affected pathways. The positive effects of pantothenate in particular mutations were also corroborated in induced neurons obtained by direct reprograming of mutant PANK2 fibroblasts. ConclusionsOur results suggest that the expression levels of mitochondrial phosphopantetheinyl-proteins are severely reduced in PKAN cells and that in selected mutations pantothenate increases the expression levels of both PANK2 and mitochondrial phosphopantetheinyl-proteins associated with remarkable improvement of cell pathophysiology.

Lipid metabolism during lactation: a review of adipose tissue-liver interactions and the development of fatty liver

2005 ◽  
Vol 72 (4) ◽  
pp. 460-469 ◽  
Author(s):  
Richard G Vernon
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Negative Energy ◽  
The Body ◽  
Unesterified Fatty Acid ◽  
Adipose Tissue Depots

Fatty acids are the major source of energy for most tissues during periods of negative energy balance; however, fatty acids can, in some circumstances, have pathological effects. Fatty acids are stored as triacylglycerols (TAG), mostly in the various adipose tissue depots of the body. However, if blood unesterified fatty acid (NEFA) levels are elevated for prolonged periods, as may occur during lactation or obesity, TAG can accumulate in other tissues including liver and muscle cells (myocytes), and this can have pathological consequences such as the development of ketosis (Grummer, 1993; Drackley et al. 2001) or type 2 diabetes (Boden & Shulman, 2002; McGarry, 2002).

scholarly journals Function of Heterologous Mycobacterium tuberculosis InhA, a Type 2 Fatty Acid Synthase Enzyme Involved in Extending C20 Fatty Acids to C60-to-C90 Mycolic Acids, during De Novo Lipoic Acid Synthesis in Saccharomyces cerevisiae

2008 ◽  
Vol 74 (16) ◽  
pp. 5078-5085 ◽  
Author(s):  
Aner Gurvitz ◽  
J. Kalervo Hiltunen ◽  
Alexander J. Kastaniotis
Keyword(s):  
Fatty Acids ◽  
Fatty Acid ◽  
Lipoic Acid ◽  
Fatty Acid Synthase ◽  
Fatty Acid Biosynthesis ◽  
De Novo ◽  
Acid Synthesis ◽  
Acid Biosynthesis ◽  
Mycolic Acids

ABSTRACT We describe the physiological function of heterologously expressed Mycobacterium tuberculosis InhA during de novo lipoic acid synthesis in yeast (Saccharomyces cerevisiae) mitochondria. InhA, representing 2-trans-enoyl-acyl carrier protein reductase and the target for the front-line antituberculous drug isoniazid, is involved in the activity of dissociative type 2 fatty acid synthase (FASII) that extends associative type 1 fatty acid synthase (FASI)-derived C20 fatty acids to form C60-to-C90 mycolic acids. Mycolic acids are major constituents of the protective layer around the pathogen that contribute to virulence and resistance to certain antimicrobials. Unlike FASI, FASII is thought to be incapable of de novo biosynthesis of fatty acids. Here, the genes for InhA (Rv1484) and four similar proteins (Rv0927c, Rv3485c, Rv3530c, and Rv3559c) were expressed in S. cerevisiae etr1Δ cells lacking mitochondrial 2-trans-enoyl-thioester reductase activity. The phenotype of the yeast mutants includes the inability to produce sufficient levels of lipoic acid, form mitochondrial cytochromes, respire, or grow on nonfermentable carbon sources. Yeast etr1Δ cells expressing mitochondrial InhA were able to respire, grow on glycerol, and produce lipoic acid. Commensurate with a role in mitochondrial de novo fatty acid biosynthesis, InhA could accept in vivo much shorter acyl-thioesters (C4 to C8) than was previously thought (>C12). Moreover, InhA functioned in the absence of AcpM or protein-protein interactions with its native FASII partners KasA, KasB, FabD, and FabH. None of the four proteins similar to InhA complemented the yeast mutant phenotype. We discuss the implications of our findings with reference to lipoic acid synthesis in M. tuberculosis and the potential use of yeast FASII mutants for investigating the physiological function of drug-targeted pathogen enzymes involved in fatty acid biosynthesis.

Metabolic alteration in healthy men with first degree type 2 diabetic relatives

2013 ◽  
Vol 154 (5) ◽  
pp. 178-186 ◽  
Author(s):  
József Pauer ◽  
Attila Fék ◽  
Barbara Buday ◽  
Botond Literáti-Nagy ◽  
Péter Pach ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Fatty Acid ◽  
Free Fatty Acid ◽  
Glucose Tolerance ◽  
Lipid Fraction ◽  
The Body ◽  
Healthy Men ◽  
Type 2 Diabetic ◽  
Degree Type

Introduction: The recognition of prediabetic patients with the genetic risk of type 2 diabetes is very important as prediabetes is the last stage when manifestation of diabetes could be prevented by life style modification or drug intervention. This suggests the need for diagnostic processes to trace the risk of patients in time. Aims: The authors looked for metabolic differences between age and BMI in adjusted healthy men with or without first degree type 2 diabetic relatives. Methods: The study included 73 healthy men (21 with and 52 without) first-degree relatives with type 2 diabetes. Results: Total body and muscle tissue glucose utilization, glucose tolerance did not differ between the two groups, but free fatty acid levels were not suppressed by glucose load in subjects with diabetic relatives. In addition the body fat content, leptin and IL-6 levels were higher, while adiponectin and the free fatty acid/adiponectin ratio were significantly lover in healthy men with diabetic relatives. In this group HDL cholesterol, and the large buoyant LDL fraction were lower whereas the high density LDL – small molecular lipid fraction was higher than those measured in subjects without diabetic relatives. Conclusions: These data suggest that deteriorations of insulin sensitivity and glucose tolerance is preceded by disturbances of fatty acid metabolism. The observed alteration in free fatty acid/adiponectin ratio, and/or the absence of free fatty acid suppression during glucose tolerance tests could be a screening tool for diabetes risk among men. Orv. Hetil., 2013, 154, 178–186.

scholarly journals Peran Leptin Terhadap Tes Toleransi Glukosa Oral pada Penderita DM Tipe 2

2020 ◽  
Vol 12 (2) ◽  
pp. 753-760
Author(s):  
Catur Ambar Wati
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Glucose Tolerance ◽  
Metabolic Diseases ◽  
Tolerance Test ◽  
The Body ◽  
Oral Glucose ◽  
Tingling Sensation

Background: DM is a group of metabolic diseases characterized by hyperglycemia that occurs due to abnormal insulin secretion, insulin action, or both. Symptoms that are complained of in diabetes mellitus sufferers are polydipsia, polyuria, polyphagia, weight loss, and tingling sensation. The oral glucose tolerance test is a test used to diagnose DM when the blood glucose level is less firm, during pregnancy, or to screen for DM or TGT. Leptin is a hormone produced by fat cells that regulate fat storage in the body and adjusts hunger to energy expenditure. Objective: to find out more about the role of leptin on TTGO in people with Type 2 diabetes. Methods: using literature studies from both national and international journals to increase knowledge and understanding of the topics discussed by summarizing the discussion topics and comparing the results presented in the article. Results: Leptin on TTGO examination in individuals with impaired glucose tolerance had a greater chance of becoming diabetes mellitus if there was no intervention in their lifestyle. Conclusion: Leptin plays a role in checking TTGO in people with Type 2 diabetes

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