Metabolic imaging of fatty kidney in diabesity: validation and dietary intervention (original) (raw)
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Triglycerides in the Human Kidney Cortex: Relationship with Body Size
PLoS ONE, 2014
Obesity is associated with increased risk for kidney disease and uric acid nephrolithiasis, but the pathophysiological mechanisms underpinning these associations are incompletely understood. Animal experiments have suggested that renal lipid accumulation and lipotoxicity may play a role, but whether lipid accumulation occurs in humans with increasing body mass index (BMI) is unknown. The association between obesity and abnormal triglyceride accumulation in non-adipose tissues (steatosis) has been described in the liver, heart, skeletal muscle and pancreas, but not in the human kidney. We used a quantitative biochemical assay to quantify triglyceride in normal kidney cortex samples from 54 patients undergoing nephrectomy for localized renal cell carcinoma. In subsets of the study population we evaluated the localization of lipid droplets by Oil Red O staining and measured 16 common ceramide species by mass spectrometry. There was a positive correlation between kidney cortex trigyceride content and BMI (Spearman R = 0.27, P = 0.04). Lipid droplets detectable by optical microscopy had a sporadic distribution but were generally more prevalent in individuals with higher BMI, with predominant localization in proximal tubule cells and to a lesser extent in glomeruli. Total ceramide content was inversely correlated with triglycerides. We postulate that obesity is associated with abnormal triglyceride accumulation (steatosis) in the human kidney. In turn, steatosis and lipotoxicity may contribute to the pathogenesis of obesity-associated kidney disease and nephrolithiasis.
Gut, 2005
Background: Hepatic steatosis is associated with obesity and type II diabetes. Proton magnetic resonance spectroscopy ( 1 H MRS) is a non-invasive method for measurement of tissue fat content, including intrahepatocellular lipids (IHCL) and intramyocellular lipids (IMCL). Patients and methods: We used 1 H MRS and whole body magnetic resonance imaging (MRI) to assess the relationship between IHCL accumulation, total body adipose tissue (AT) content/distribution, and IMCL content in 11 subjects with biopsy proven hepatic steatosis and 23 normal volunteers. Results: IHCL signals were detectable in all subjects but were significantly greater in hepatic steatosis (geometric mean (GM) 11.5 (interquartile range (IQR) 7.0-39.0)) than in normal volunteers (GM 2.7 (IQR 0.7-9.3); p = 0.02). In the study group as a whole, IHCL levels were significantly greater in overweight compared with lean subjects (body mass index (BMI) .25 kg/m 2 (n = 23): GM 7.7 (IQR 4.0-28.6) v BMI ,25 kg/m 2 (n = 11): GM 1.3 (IQR 0.3-3.6; p = 0.004)). There was a significant association between IHCL content and indices of overall obesity (expressed as a percentage of body weight) for total body fat (p = 0.001), total subcutaneous AT (p = 0.007), and central obesity (subcutaneous abdominal AT (p = 0.001) and intra-abdominal AT (p = 0.001)), after allowing for sex and age. No correlation between IHCL content and IMCL was observed. A significant correlation was observed between serum alanine aminotransferase and liver fat content (r = 0.57, p = 0.006). Conclusions: Our results suggest that hepatic steatosis appears to be closely related to body adiposity, especially central obesity. MRS may be a useful method for monitoring IHCL in future interventional studies.
Metabolites, 2021
Severe obesity is a major risk for chronic kidney disease (CKD). Early detection and careful monitoring of renal function are critical for the prevention of CKD during obesity, since biopsies are not performed in patients with CKD and diagnosis is dependent on the assessment of clinical parameters. To explore whether distinct lipid and metabolic signatures in obesity may signify early stages of pathogenesis toward CKD, liquid chromatography-mass spectrometry (LC-MS) and gas chromatography-high resolution accurate mass-mass spectrometry (GC-HRAM-MS) analyses were performed in the serum and the urine of severely obese patients with and without CKD. Moreover, the impact of bariatric surgery (BS) in lipid and metabolic signature was also studied, through LC-MS and GC-HRAM-MS analyses in the serum and urine of patients with severe obesity and CKD before and after undergoing BS. Regarding patients with severe obesity and CKD compared to severely obese patients without CKD, serum lipidome ...
Non-invasive Quantification of Triglyceride Content in Steatotic Rat Livers by 1H-MRS
Academic Radiology, 2011
The aims of this study were to explore the relationship between triglyceride (TG) and water in steatotic rat livers and to accordingly test the validity of the currently used steatosis calculation methods from magnetic resonance spectra. The approximations commonly used to derive steatosis degrees from magnetic resonance spectra include the generic types TG/water and TG/(TG + water).
Legacy of the Tehran Lipid and Glucose Study: Chronic Kidney Disease
International Journal of Endocrinology and Metabolism, 2018
Context: Chronic kidney disease (CKD), is correlated with a substantial upsurge in mortality and morbidity worldwide. In this review, we aimed to review the 20-year-findings on CKD of the Tehran lipid and glucose study (TLGS). Evidence Acquisition: We conducted a systematic review of all studies on CKD that had been performed in the context of TLGS. Results: Age adjusted prevalence of CKD, according to estimated glomerular filtration rate (eGFR) assessed with the two abbreviated equations of the modification of diet in renal disease (MDRD) and the CKD epidemiology collaboration (CKD-EPI) were 11.3% (95% confidence interval (CI): 10.7, 12.0) and 8.5% (95% CI: 7.9, 9.1), respectively. Using MDRD equation, over a mean follow up of 9.9 years, the incidence density rates of CKD were 285.3 person years in women and 132.6 per 10000 person-years in men. Studies on the TLGS population documented that abdominal adiposity defined as waist circumference (WC) categories (P for trend < 0.02) and waist gain in men (hazard ratio (HR) = 1.7, CI: 1.3, 2.2) significantly affected CKD development. Also, CKD had a significant effect on coronary heart disease (CHD) only in participants with low body mass index (HR = 2.06; CI: 1.28, 3.31 and HR = 2.56; CI: 1.04, 6.31 in men and women, respectively). Moreover, CKD was among the strongest independent predictors of stroke (HR = 2.01, CI: 1.22, 3.33). Also, compared to diabetic patients, an abnormal ECG was more prevalent in moderate CKD (P = 0.02). Conclusions: Increased waist circumference and waist gain (only in men) were associated with developing CKD in the TLGS population. CKD was an independent predictor of CHD (in lean individuals) and stroke.
Quantification of renal steatosis in type II diabetes mellitus using dixon-based MRI
Journal of magnetic resonance imaging : JMRI, 2016
To evaluate renal lipid content in subjects with and without type II diabetes mellitus (DM2) using Dixon-based magnetic resonance imaging (MRI). This retrospective study was approved by the Institutional Review Board and compliant with the Health Insurance Portability and Accountability Act. Sixty-nine adults with or without DM2 (n = 29, n = 40) underwent 3T MRI of the abdomen using 3D multiecho Dixon gradient-echo acquisition and proton-density fat fraction (FF) reconstruction. FF values were recorded within segmented regions of interest in the kidneys and liver. The FF measurement error was estimated from the within-subject difference between the right and left kidneys using Bland-Altman analysis. Correlation between renal FF, hepatic FF, and body mass index (BMI) was evaluated. The association between renal FF and DM2 was evaluated by Wilcoxon rank sum test as well as by multivariate regression to correct for potential confounding effects of age, sex, BMI, creatinine, and hepatic...
International Journal of Molecular Sciences
Chronic kidney disease (CKD) is associated with atherogenic dyslipidemia. Our aim was firstly to investigate patterns of fatty acids (FA) composition through various stages of CKD, and secondly, to evaluate the effect of CKD-specific FA disturbances on the expression of genes related to lipid metabolism at a cellular level. Serum FA composition was analyzed in 191 patients with consecutive severity stages of CKD, and 30 healthy controls free from CKD. Next, HepG2 human hepatic cells were treated with major representatives of various FA groups, as well as with FA extracted from a mix of serums of controls and of CKD stage 5 patients. Across worsening stages of CKD severity, there was an increasing monounsaturated FA (MUFA) content. It was associated with a concomitant decrease in n-3 and n-6 polyunsaturated FA. The incubation of hepatocytes with FA from CKD patients (compared to that of healthy subjects), resulted in significantly higher mRNA levels of genes involved in FA synthesis ...
The Iberian pig fed with high-fat diet: a model of renal disease in obesity and metabolic syndrome
International Journal of Obesity, 2019
Background The pathogenesis of renal disease in the context of overweight/obesity, metabolic syndrome, and insulin resistance is not completely understood. This may be due to the lack of a definitive animal model of disease, which limits our understanding of obesity-induced renal damage. We evaluated the changes in renal histology and lipid deposits induced by obesity in a model of insulin resistance: the Iberian swine fed with fat-enriched food. Methods Twenty-eight female sows were randomized to standard (SD) or high-fat diet (HFD: 6.8% of saturated fat) for 100 days. Weight, adiposity, analytics, oral glucose tolerance tests, and measured renal function were determined. Renal histology and lipid deposits in renal tissue were analyzed. Results Animals on HFD developed obesity, hypertension, high levels of LDL cholesterol, triglycerides, insulin resistance, and glomerular hyperfiltration. No animal developed overt diabetes. Animals on HFD showed "diabetoid changes", including mesangial expansion [21.40% ± 4 vs.13.20% ± 4.0, p < 0.0001], nodular glomerulosclerosis [7.40% ± 7, 0.75 vs. 2.40% ± 4.7, p = 0.02], and glomerulomegaly (18% vs. 10%, p = 0.010) than those on SD. Tubular atrophy, interstitial fibrosis, inflammation, arteriolar hyalinosis, or fibrointimal thickening were mild and similar between groups. Triglyceride content in renal tissue was higher in animals on HFD than in SD (15.4% ± 0.5 vs. 12.7% ± 0.7; p < 0.01). Conclusions Iberian pigs fed with fat-enriched food showed diabetoid changes and glomerulomegaly as observed in obese humans making this model suitable to study obesity-induced renal disease.
Obesity-Related Chronic Kidney Disease—The Role of Lipid Metabolism
Metabolites, 2015
Obesity is an independent risk factor for chronic kidney disease (CKD). The mechanisms linking obesity and CKD include systemic changes such as high blood pressure and hyperglycemia, and intrarenal effects relating to lipid accumulation. Normal lipid metabolism is integral to renal physiology and disturbances of renal lipid and energy metabolism are increasingly being linked with kidney disease. AMP-activated protein kinase (AMPK) and acetyl-CoA carboxylase (ACC) are important regulators of fatty acid oxidation, which is frequently abnormal in the kidney with CKD. A high fat diet reduces renal AMPK activity, thereby contributing to reduced fatty acid oxidation and energy imbalance, and treatments to activate AMPK are beneficial in animal models of obesity-related CKD. Studies have found that the specific cell types affected by excessive lipid accumulation are proximal tubular cells, podocytes, and mesangial cells. Targeting disturbances of renal energy metabolism is a promising approach to addressing the current epidemic of obesity-related kidney disease.