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 Evaluation of the In Vitro Damage Caused by Lipid Factors on Stem Cells from a Female Rat Model of Type 2 Diabetes/Obesity and Stress Urinary Incontinence

2020 ◽  
Vol 21 (14) ◽  
pp. 5045
Author(s):  
Istvan Kovanecz ◽  
Robert Gelfand ◽  
Sheila Sharifzad ◽  
Alec Ohanian ◽  
William DeCastro ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Urinary Incontinence ◽  
Stem Cell ◽  
Stress Urinary Incontinence ◽  
Rat Model ◽  
Male Rats ◽  
Female Stress Urinary Incontinence ◽  
Female Rat

Human stem cell therapy for type 2 diabetes/obesity (T2D/O) complications is performedwith stem cell autografts, exposed to the noxious T2D/O milieu, often with suboptimal results.We showed in the Obese Zucker (OZ) rat model of T2D/O that when their muscle-derived stemcells (MDSC) were from long-term T2D/O male rats, their repair ecacy for erectile dysfunctionwas impaired and were imprinted with abnormal gene- and miR-global transcriptional signatures(GTS). The damage was reproduced in vitro by short-term exposure of normal MDSC to dyslipidemicserum, causing altered miR-GTS, fat infiltration, apoptosis, impaired scratch healing, and myostatinoverexpression. Similar in vitro alterations occurred with their normal counterparts (ZF4-SC) fromthe T2D/O rat model for female stress urinary incontinence, and with ZL4-SC from non-T2D/O leanfemale rats. In the current work we studied the in vitro eects of cholesterol and Na palmitate aslipid factors on ZF4-SC and ZL4-SC. A damage partially resembling the one caused by the femaledyslipidemic serum was found, but diering between both lipid factors, so that each one appears tocontribute specifically to the stem cell damaging eects of dyslipidemic serum in vitro and T2D/Oin vivo, irrespective of gender. These results also confirm the miR-GTS biomarker value forMDSC damage.

scholarly journals Type 2 Diabetes and its Effects on MicroRNA-155 and MicroRNA-133a Expression in Lung Tissue of Male Rats

2021 ◽  
Author(s):  
Maria Khezri ◽  
Reza Rahbarghazi ◽  
Mahdi Ahmadi ◽  
Siamak Sandoghchian ◽  
Alireza Nourazarian ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Lung Tissue ◽  
Inflammatory Cells ◽  
Normal Structure ◽  
Lung Parenchyma ◽  
Diabetic Rats ◽  
Normal Diet ◽  
Male Rats ◽  
Control Group

Abstract Background: The presence of an extensive vascular extent and large amounts of collagen and elastin in lung tissue make the lung parenchyma vulnerable to damage in diabetes. However, there are few studies on the pathophysiological effects of diabetes on lung tissue. In this study, we investigated the effects of type 2 diabetes on lung tissue pathology and the expression of miRNA-155 and miRNA-133a in lung tissue of male rats.Methods: In this study, 14 male rats were divided into a control group and a group with diabetes. The group with diabetes received a high-fat diet and a single dose of streptozotocin for one month. After induction of T2D, the rats received a normal diet for the next four weeks. At week 8, the rats were euthanized, and lung tissue was collected to measure microRNAs and examine tissue changes.Results: When lung tissue sections from diabetic rats were examined, the normal structure of the alveoli and alveolar sacs and bronchioles was disturbed. The thickness of interalveolar septa was increased due to the infiltration of inflammatory cells. The extensive alveolar collapse was the main cause of lung tissue structure disruption, and the accumulation of inflammatory cells and exudate secretions resulted in an interstitial pneumonia-like appearance. The expression of miRNA-155 was increased, and the expression of miRNA-133a was decreased in the lungs of diabetic rats compared with control rats.Conclusion: We found significant changes in the lung tissue of diabetic rats. By studying changes in the expression of microRNAs in diabetes, they can be a diagnostic and therapeutic biomarker in the lungs of patients with diabetes.

scholarly journals Darapladib inhibits atherosclerosis development in type 2 diabetes mellitus Sprague-Dawley rat model

2018 ◽  
Vol 52 (2) ◽  
pp. 69-75 ◽  
Author(s):  
Titin Andri Wihastuti ◽  
Teuku Heriansyah ◽  
Hanifa Hanifa ◽  
Sri Andarini ◽  
Zuhrotus Sholichah ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Foam Cells ◽  
Male Rats ◽  
Sprague Dawley ◽  
Early Stages ◽  
Sprague Dawley Rat

AbstractObjective. Increase in the low-density lipoprotein (LDL) level in diabetes mellitus and atherosclerosis is related to lipoprotein associated phospholipase A2 (Lp-PLA2). Lp-PLA2 is an enzyme that produces lysophosphatidylcholine (LysoPC) and oxidized nonesterified fatty acids (oxNEFA). LysoPC regulates inflammation mediators, including intra-cellular adhesion molecule-1 (ICAM-1). Darapladib is known as a Lp-PLA2 specific inhibitor. The aim of this study was to reveal the effect of darapladib on the foam cell number, inducible nitric oxide synthase (iNOS), and ICAM-1 expression in aorta at early stages of the atherosclerosis in type 2 diabetes mellitus Sprague-Dawley rat model.Methods. Thirty Sprague-Dawley male rats were divided into 3 main groups: control, rats with type 2 diabetes mellitus (T2DM), and T2DM rats treated with darapladib (T2DM-DP). Each group was divided into 2 subgroups according the time of treatment: 8-week and 16-week treatment group. Fasting blood glucose, insulin resistance, and lipid profile were measured and analyzed to ensure T2DM model. The foam cells number were detected using hematoxylin-eosin (HE) staining and the expression of iNOS and ICAM-1 was analyzed using double immunofluorescence staining.Results. Induction of T2DM in male Sprague-Dawley rats after high fat diet and streptozotocin injection was confirmed by elevated levels of total cholesterol and LDL and increased fasting glucose and insulin levels compared to controls after both times of treatment. Moreover, T2DM in rats induced a significant increase (p<0.05) in the foam cells number and iNOS and ICAM-1 expression in aorta compared to controls after both treatment times. Darapladib treatment significantly reduced (p<0.05) foam cells number as well as iNOS expression in aorta in rats with T2DM after both treatment times. A significant decrease (p<0.05) in ICAM-1 expression in aorta was observed after darapladib treatment in rats with T2DM only after 8 weeks of treatment.Conclusion. Our data indicate that darapladib can decrease the foam cells number, iNOS, and ICAM-1 expression in aorta at the early stages of atherosclerosis in T2DM rat model.

scholarly journals Boldine Does Not Modify Gender Specific Wound Healing in Zucker Diabetic Rats

2018 ◽  
Vol 13 (11) ◽  
pp. 1934578X1801301
Author(s):  
Renata Köhlerová ◽  
Eva Čermáková ◽  
Milena Hajzlerová
Keyword(s):  
Type 2 Diabetes ◽  
Diabetic Rats ◽  
Female Rats ◽  
Male Rats ◽  
Positive Effects ◽  
Natural Alkaloid ◽  
Anti Inflammatory ◽  
Antioxidant Effects

Boldine is a natural alkaloid with anti-inflammatory and antioxidant effects. It reduces glycemia and decreases blood pressure in rats with type 1 diabetes. We have also studied whether boldine has anti-inflammatory and antioxidant effects in rats with type 2 diabetes and whether it can improve healing of their skin wounds, a serious comorbidity of type 2 diabetes. This work also compares lean and obese Zucker diabetic rats, including a comparison of both sexes. After skin excisions, the wounded animals received granules containing boldine ad libitum. The weights of rats, amount of consumed food and wound size were measured regularly. Scar and internal organs were removed and analyzed. Further, the tensile strength of the scar was tested and hydroxyproline content (a marker of collagen) measured. We have not confirmed previously published positive effects of boldine, but we observed important differences between gender and between genotypes. Male rats had higher body weight, liver, kidney and spleen than female rats. Furthermore, their wounds took longer to heal with bigger scar areas.

scholarly journals The Biological Impacts of Sitagliptin on the Pancreas of a Rat Model of Type 2 Diabetes Mellitus: Drug Interactions with Metformin

Biology ◽  
2019 ◽  
Vol 9 (1) ◽  
pp. 6 ◽  
Author(s):  
Lamiaa M. Shawky ◽  
Ahmed A. Morsi ◽  
Eman El Bana ◽  
Safaa Masoud Hanafy
Keyword(s):  
Diabetes Mellitus ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Rat Model ◽  
Cell Damage ◽  
Diabetic Rats ◽  
Male Rats ◽  
Control Group ◽  
Dipeptidyl Peptidase 4

Sitagliptin, a dipeptidyl peptidase-4 (DPP-4) inhibitor, is a beneficial class of antidiabetic drugs. However, a major debate about the risk of developing pancreatitis is still existing. The aim of the work was to study the histological and immunohistochemical effects of sitagliptin on both endocrine and exocrine pancreases in a rat model of type 2 diabetes mellitus and to correlate these effects with the biochemical findings. Moreover, a possible synergistic effect of sitagliptin, in combination with metformin, was also evaluated. Fifty adult male rats were used and assigned into five equal groups. Group 1 served as control. Group 2 comprised of untreated diabetic rats. Group 3 diabetic rats received sitagliptin. Group 4 diabetic rats received metformin. Group 5 diabetic rats received both combined. Treatments were given for 4 weeks after the induction of diabetes. Blood samples were collected for biochemical assay before the sacrification of rats. Pancreases were removed, weighed, and were processed for histological and immunohistochemical examination. In the untreated diabetic group, the islets appeared shrunken with disturbed architecture and abnormal immunohistochemical reactions for insulin, caspase-3, and inducible nitric oxide synthase (iNOS). The biochemical findings were also disturbed. Morphometrically, there was a significant decrease in the islet size and islet number. Treatment with sitagliptin, metformin, and their combination showed an improvement, with the best response in the combined approach. No evidence of pancreatic injury was identified in the sitagliptin-treated groups. In conclusion, sitagliptin had a cytoprotective effect on beta-cell damage. Furthermore, the data didn’t indicate any detrimental effects of sitagliptin on the exocrine pancreas.

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 Phenotypic Characterization of LEA Rat: A New Rat Model of Nonobese Type 2 Diabetes

2013 ◽  
Vol 2013 ◽  
pp. 1-9 ◽  
Author(s):  
Tadashi Okamura ◽  
Xiang Yuan Pei ◽  
Ichiro Miyoshi ◽  
Yukiko Shimizu ◽  
Rieko Takanashi-Yanobu ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Cell Mass ◽  
Spontaneous Diabetes ◽  
Tubular Epithelial Cell ◽  
The Body ◽  
Male Rats ◽  
Phenotypic Characterization ◽  
Dependent Manner ◽  
Long Evans

Animal models have provided important information for the genetics and pathophysiology of diabetes. Here we have established a novel, nonobese rat strain with spontaneous diabetes, Long-Evans Agouti (LEA) rat derived from Long-Evans (LE) strain. The incidence of diabetes in the males was 10% at 6 months of age and 86% at 14 months, while none of the females developed diabetes. The blood glucose level in LEA male rats was between 200 and 300 mg/dl at 120 min according to OGTT. The glucose intolerance in correspondence with the impairment of insulin secretion was observed in male rats, which was the main cause of diabetes in LEA rats. Histological examination revealed that the reduction ofβ-cell mass was caused by progressive fibrosis in pancreatic islets in age-dependent manner. The intracytoplasmic hyaline droplet accumulation and the disappearance of tubular epithelial cell layer associated with thickening of basement membrane were evident in renal proximal tubules. The body mass index and glycaemic response to exogenous insulin were comparable to those of control rats. The unique characteristics of LEA rat are a great advantage not only to analyze the progression of diabetes, but also to disclose the genes involved in type 2 diabetes mellitus.

scholarly journals Changes in C-reactive protein levels before type 2 diabetes and cardiovascular death: the Whitehall II study

2010 ◽  
Vol 163 (1) ◽  
pp. 89-95 ◽  
Author(s):  
A G Tabák ◽  
M Kivimäki ◽  
E J Brunner ◽  
G D Lowe ◽  
M Jokela ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Disease Onset ◽  
Self Report ◽  
Incident Diabetes ◽  
Oral Glucose ◽  
C Reactive Protein ◽  
Reactive Protein ◽  
Age Related

ObjectiveProspective studies show that high C-reactive protein (CRP) levels predict diabetes and cardiovascular disease (CVD), but changes in this marker preceding disease onset are not well characterized. This study describes CRP trajectories prior to type 2 diabetes onset and fatal CVD.MethodsIn a prospective cohort of 7350 British civil servants (70% male, mean age 51 years), 558 incident type 2 diabetes cases (75-g oral glucose tolerance test, doctor's diagnosis, or self-report) and 125 certified fatal cardiovascular events were observed during a median follow-up of >14 years. Trajectories of logarithmically transformed CRP levels prior to incident diabetes or fatal cardiovascular event (cases), or the end of follow-up (controls) were calculated using multilevel modeling.ResultsBaseline CRP levels were higher among participants who developed diabetes (median (interquartile range) 1.44 (2.39) vs 0.78 (1.21) mg/l) or fatal CVD (1.49 (2.47) vs 0.84 (1.30) mg/l) compared with controls (bothP<0.0001). In models adjusted for age, sex, body mass index, ethnicity, and employment grade, CRP levels increased with time among both incident diabetes cases and controls (P<0.0001), but this increase was less steep for cases group (P<0.05). CRP levels followed increasing linear trajectories in fatal cardiovascular cases and controls (P<0.0001) with no slope difference between the groups.ConclusionsCRP levels were higher among those who subsequently developed diabetes or died from CVD. For type 2 diabetes, age-related increase in CRP levels was less steep in the cases group than in controls, whereas for fatal CVD these trajectories were parallel.

scholarly journals Development and characterization of a novel rat model of type 2 diabetes mellitus: the UC Davis type 2 diabetes mellitus UCD-T2DM rat

2008 ◽  
Vol 295 (6) ◽  
pp. R1782-R1793 ◽  
Author(s):  
Bethany P. Cummings ◽  
Erin K. Digitale ◽  
Kimber L. Stanhope ◽  
James L. Graham ◽  
Denis G. Baskin ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Type 2 Diabetes ◽  
Type 2 Diabetes Mellitus ◽  
Glucose Tolerance ◽  
Rat Model ◽  
Age Of Onset ◽  
Female Rats ◽  
Β Cell

The prevalence of type 2 diabetes (T2DM) is increasing, creating a need for T2DM animal models for the study of disease pathogenesis, prevention, and treatment. The purpose of this project was to develop a rat model of T2DM that more closely models the pathophysiology of T2DM in humans. The model was created by crossing obese Sprague-Dawley rats with insulin resistance resulting from polygenic adult-onset obesity with Zucker diabetic fatty-lean rats that have a defect in pancreatic β-cell function but normal leptin signaling. We have characterized the model with respect to diabetes incidence; age of onset; longitudinal measurements of glucose, insulin, and lipids; and glucose tolerance. Longitudinal fasting glucose and insulin data demonstrated progressive hyperglycemia (with fasting and fed glucose concentrations >250 and >450 mg/dl, respectively) after onset along with hyperinsulinemia resulting from insulin resistance at onset followed by a progressive decline in circulating insulin concentrations, indicative of β-cell decompensation. The incidence of diabetes in male and female rats was 92 and 43%, respectively, with an average age of onset of 6 mo in males and 9.5 mo in females. Results from intravenous glucose tolerance tests, pancreas immunohistochemistry, and islet insulin content further support a role for β-cell dysfunction in the pathophysiology of T2DM in this model. Diabetic animals also exhibit glycosuria, polyuria, and hyperphagia. Thus diabetes in the UC Davis-T2DM rat is more similar to clinical T2DM in humans than in other existing rat models and provides a useful model for future studies of the pathophysiology, treatment, and prevention of T2DM.

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

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