- Chronic hypercortisolism causes more persistent visceral adiposity than HFD-induced obesity. [Journal Article]
- JEJ Endocrinol 2019 May 01
- Excessive and prolonged glucocorticoid (GC) exposure, resulting from either prescribed or endogenous hypercortisolism, is associated with a high cardiovascular and metabolic burden (Cushing's syndrom…
Excessive and prolonged glucocorticoid (GC) exposure, resulting from either prescribed or endogenous hypercortisolism, is associated with a high cardiovascular and metabolic burden (Cushing's syndrome). Although previous studies in humans and mice have reported heterogeneous data about the persistence of metabolic syndrome features after remission of hypercortisolism, there is still controversy as to whether this is due to the deleterious changes induced by GCs during active disease or the result of various other factors interfering in the recovery period. In order to study metabolic effects after remission, we used a reversible mouse model of corticosterone (CORT) (100 µg/ml) administration in drinking water for five weeks, followed by a 10-week recovery period. We compared CORT-induced effects at these time points with a high-fat diet-treated group (HFD 45%) and a vehicle group (VEH). Plasma CORT, 11β-HSD activity, food intake, glucose levels, interscapular brown adiposity, hepatic triglycerides and muscle mass were found altered during CORT treatment but normalized after recovery. Although hyperinsulinemia and insulin resistance were increased during CORT and HFD treatment, insulin homeostasis remained altered following the recovery period only in CORT-treated mice. Subcutaneous and visceral adipose tissues (SAT and VAT) were enlarged during HFD and CORT treatment as measured by MRI. However, increased muscle lipid content, adiposity and macrophage infiltration in VAT were only present in the CORT group following recovery. Taken together, CORT-induced insulin alterations were more potent than HFD-induced ones during the same period of treatment, and also more persistent long term . Moreover, we demonstrated that CORT treatment induces more long-lasting visceral adipose tissue enlargement than HFD.
- Ketogenic diet in combination with voluntary exercise impacts markers of hepatic metabolism and oxidative stress in male and female Wistar rats. [Journal Article]
- APAppl Physiol Nutr Metab 2019 May 22
- Ketogenic diets (KD) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise are unknown. We investigated the effects of a KD vs a 'Western' diet (WD) …
Ketogenic diets (KD) are shown to benefit hepatic metabolism; however, their effect on the liver when combined with exercise are unknown. We investigated the effects of a KD vs a 'Western' diet (WD) on markers of hepatic lipid metabolism and oxidative stress in exercising rats. Male and female Wistar rats with access to voluntary running wheels were randomized to three groups (n= 8-14 per group): standard chow (SC; 17% Fat), WD (42% Fat) or KD (90.5% Fat) for 7 weeks. Body fat percentage (BF%) was increased in WD and KD vs SC, although KD females displayed lower BF% vs WD (p≤0.05). Liver triglycerides were higher in KD and WD vs SC, but were attenuated in KD females vs WD (p≤0.05). KD suppressed hepatic markers of de novo lipogenesis (FAS, ACC) and increased markers of mitochondrial biogenesis/content (PGC-1α, TFAM and citrate synthase activity). KD also increased the hepatic GPx1 and lowered oxidized glutathione. Females rats exhibited elevated hepatic markers of mitochondrial biogenesis (TFAM), mitophagy (LC3II/I ratio, ATG 12:5) and cellular energy homeostasis (pAMPK/AMPK) vs males. These data highlight that KD and exercise beneficially impacts hepatic metabolism and oxidative stress and merits further investigation. • Ketogenic diet feeding combined with exercise improved hepatic oxidative stress, suppressed markers of de novo lipogenesis, increased markers of mitochondrial content vs western diet feeding. • Males and females responded similarly to combined ketogenic diet feeding and exercise. • Female rats exhibited elevated hepatic markers of autophagy/mitophagy and energy homeostasis compared with male rats.
- Relationship between DXA measured metrics of adiposity and glucose homeostasis; An analysis of the NHANES data. [Journal Article]
- PlosPLoS One 2019; 14(5):e0216900
- CONCLUSIONS: Body fat % on DXA is an imaging biomarker for insulin resistance. Incorporating this important information into DXA acquisitions and reporting frameworks may allow for this information to be available to providers who refer patients for these imaging studies.
- Health outcomes of a high fructose intake: the importance of physical activity. [Journal Article]
- JPJ Physiol 2019 May 22
- Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these…
Fructose metabolism is generally held to occur essentially in cells of the small bowel, the liver, and the kidneys expressing fructolytic enzymes (fructokinase, aldolase B and a triokinase). In these cells, fructose uptake and fructolysis are unregulated processes, resulting in the generation of intracellular trioses-phosphate proportionate to fructose intake. Trioses-phosphate are then processed into lactate, glucose, and fatty acids to serve as metabolic substrates in other cells of the body. With small oral loads, fructose is mainly metabolized in the small bowel, while with larger loads fructose reaches the portal circulation and is largely extracted by the liver. A small portion however escapes liver extraction and is metabolized either in the kidneys or in other tissues through yet unspecified pathways. In sedentary subjects, consumption of a fructose-rich diet for several days stimulates hepatic de novo lipogenesis, increases intrahepatic fat and blood triglycerides concentrations, and impairs insulin effects on hepatic glucose production. All these effects can be prevented when high fructose intake is associated with increased levels of physical activity. There is also evidence that, during exercise, fructose carbons are efficiently transferred to skeletal muscle as glucose and lactate to be used for energy production. Glucose and lactate formed from fructose can also contribute to the re-synthesis of muscle glycogen after exercise. We therefore propose that the deleterious health effects of fructose are tightly related to an imbalance between fructose energy intake on one hand, and whole-body energy output related to a low physical activity on the other hand. Modulation of fructose metabolism by fructose intake and muscle energy output. In conditions of low fructose intake (Abstract figure A), available data suggest that fructose is primarily metabolized in the gut and, to a lesser extent, in the liver. Fructose metabolized in these organs then recirculates as glucose and lactate intermediates to be distributed to the periphery. With increasing fructose intake (Abstract figure B), intestinal fructose metabolism becomes saturated and fructose is mostly extracted by the liver where it is still converted into metabolic intermediates. When total energy output is high, fructose conversion into glucose and lactate remain the preferred, most energy-efficient disposal routes as both intermediates can provide energy to working muscle. When total energy output is low (Abstract figure C), however, the mismatch between fructose input and energy output forces the diversion of some fructose into lipids. According to this model, fructose deleterious effects on health would only appear in conditions of chronically high fructose intake associated with low physical activity. IHCL: intrahepatocellular lipids; TRL-TG: triglycerides in triglycerides-rich lipoproteins.2 This article is protected by copyright. All rights reserved.
- YKL-40 promotes the progress of atherosclerosis independent of lipid metabolism in apolipoprotein E-/- mice fed a high-fat diet. [Journal Article]
- HVHeart Vessels 2019 May 21
- YKL-40 is recently regarded as a pro-inflammatory cytokine involved in the pathological process of atherosclerosis and lipid metabolism. However, whether YKL-40 can directly influence the development…
YKL-40 is recently regarded as a pro-inflammatory cytokine involved in the pathological process of atherosclerosis and lipid metabolism. However, whether YKL-40 can directly influence the development of atherosclerosis and levels of lipid parameters is unknown. The aim of this study is to explore the effects of YKL-40 on atherosclerotic features, the levels of serum lipids, and biomarkers in apolipoprotein (E)-deficient (ApoE-/-) mice fed a high-fat diet. ApoE-/- mice were injected with a recombinant adenovirus expressing mouse YKL-40 or control adenovirus through the caudal vein. The levels of serum YKL-40, interleukin-6 (IL-6), tumour necrosis factor-alpha (TNF-alpha), matrix metalloproteinase-9 (MMP-9), and soluble vascular cell-adhesion molecule 1 (sVCAM-1) were measured by ELISA. Lipid metabolism parameters were measured using immunoturbidimetric assay. The size of plaque area in aorta was evaluated by Oil Red O and hematoxylin/eosin (HE) staining. The content of collagen fibers was stained with Masson, and the content of macrophages and smooth muscle cells (SMCs) in atherosclerotic lesions was investigated by immunohistochemistry. The serum levels of total cholesterol and triglycerides were similar between these two groups. Compared with the control, the levels of serum YKL-40, IL-6, TNF-alpha, MMP-9, plaque size, and macrophages in plaques were significantly increased in mice with adenovirus overexpressing YKL-40. However, the content of collagen fibers and SMCs was remarkably decreased in mice with adenovirus overexpressing YKL-40 than that in control. YKL-40 prompts the progress of atherosclerosis maybe involved with its role of pro-inflammation, but does not affect lipid metabolism in ApoE-/- mice fed a high-fat diet.
- Atherogenesis in Psoriasis: Evaluation of the Serum Activities of Non-high-density Lipoprotein Cholesterol and Other Lipids Among Newly Diagnosed Psoriasis Patients. [Journal Article]
- CCureus 2019 Mar 07; 11(3):e4203
- Introduction Psoriasis is a chronic inflammatory skin disorder which commonly affects people aged between 15-25 years with a 2-3 % prevalence rate throughout the world. Psoriasis is a systemic inflam…
Introduction Psoriasis is a chronic inflammatory skin disorder which commonly affects people aged between 15-25 years with a 2-3 % prevalence rate throughout the world. Psoriasis is a systemic inflammatory disease associated with severe co-morbidities that include cardiovascular risk. Although changes in the atherogenic lipids among psoriasis patients is already documented, very little is known about their role in atherogenesis among the new onset cases of psoriasis. Hence, this study is undertaken to assess the activities of non-high-density lipoprotein cholesterol (non-HDL-C) and other lipids among newly diagnosed psoriasis patients. Methods The study included 25 new onset cases of psoriasis patients aged between 20-60 years (mean age 38.2 years) attending the Dermatology outpatient department (OPD) of the Chalmeda Anandrao Institute of Medical Sciences (CAIMS), Karimnagar, Telangana, India, a tertiary care teaching hospital. An equal number of healthy individuals were included as controls. Blood was collected from all the subjects included in the study and was analyzed for various lipid parameters that included total cholesterol (TC), HDL-C, and triglycerides. The non-HDL-C and low-density lipoprotein cholesterol (LDL-C) were later calculated manually by using the standard formulae. The data were tabulated using Microsoft Excel and was analyzed for their statistical significance using the Student t-test. Results The results demonstrated a statistically significant difference in the lipid parameters between the cases and controls. Among the parameters measured, the pro-atherogenic lipids including the LDL-C and non-HDL-C activities among the cases (LDL-C 171.46±17.13, p=0.0002; non-HDL-C 213.27±20.17, p ≤ 0.0001) and controls (LDL-C 91.04±11.41, p=0.0002; Non-HDL-C 119.0± 12.28, p ≤ 0.0001) were found to be statistically significant. The ratios of non-HDL-C to HDL-C and total cholesterol to HDL-C both among the cases (7.10±0.1, 8.13±1.2) and control groups (3.05±0.30, 4.03±0.42) were also showing a statistically significant difference. Conclusion The results clearly demonstrate the significance of the evaluation of lipids among newly diagnosed cases of psoriasis patients. The activities of different lipoproteins including the non-HDL-C and LDL-C revealed an increase among the psoriasis patients. The ratios of non-HDL-C to HDL-C and TC to HDL-C also showed significant variability. Further, to establish their clinical utility in the development of cardiovascular disease (CVD), and to manage appropriately, a regular follow-up of such parameters both before and after initiation of treatment is required.
- Beneficial effects of losartan or telmisartan on the local hepatic renin-angiotensin system to counter obesity in an experimental model. [Journal Article]
- WJWorld J Hepatol 2019 Apr 27; 11(4):359-369
- CONCLUSIONS: Modulation of the intrahepatic RAS, with favored involvement of the ACE2/rMAS axis over the ACE1/AT1r axis after losartan or telmisartan treatments, caused hepatic and metabolic beneficial effects as demonstrated by reduced hepatic triacylglycerol levels coupled with reduced PLIN 2 expression and improved glycemic control.
- Association between lipid accumulation product and diabetic retinopathy based on a community-based survey in Chinese with type 2 diabetes. [Journal Article]
- DMDiabetes Metab Syndr Obes 2019; 12:513-518
- CONCLUSIONS: Higher central lipid accumulation in Chinese diabetics is related to the lower risk of DR, suggesting that LAP may be useful for identifying type 2 diabetes mellitus patients who are at risk for DR.
- Lysosomal Acid Lipase Deficiency Leading to Liver Cirrhosis: a Case Report of a Rare Variant Mutation. [Journal Article]
- AHAnn Hepatol 2019 Jan - Feb; 18(1):230-235
- Lysosomal acid lipase deficiency is a poorly diagnosed genetic disorder, leading to accumulation of cholesterol esters and triglycerides in the liver, with progression to chronic liver disease, dysli…
Lysosomal acid lipase deficiency is a poorly diagnosed genetic disorder, leading to accumulation of cholesterol esters and triglycerides in the liver, with progression to chronic liver disease, dyslipidemia, and cardiovascular complications. Lack of awareness on diagnosis of this condition may hamper specific treatment, which consists on enzymatic replacement. It may prevent the progression of liver disease and its complications. We describe the case of a 53-year-old Brazilian man who was referred to our center due to the diagnosis of liver cirrhosis of unknown etiology. He was asymptomatic and had normal body mass index. He had dyslipidemia, and family history of myocardial infarction and stroke. Abdominal imaging tests showed liver cirrhosis features and the presence of intrahepatic calcifications. Initial investigation of the etiology of the liver disease was not elucidated, but liver biopsy showed microgoticular steatosis and cholesterol esters deposits in Kuppfer cells. The dosage of serum lysosomal acid lipase was undetectable and we found the presence of a rare homozygous mutation in the gene associated with the lysosomal acid lipase deficiency, (allele c.386A > G homozygous p.H129R).
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- Genome analysis and pleiotropy assessment using causal networks with loss of function mutation and metabolomics. [Journal Article]
- BGBMC Genomics 2019 May 21; 20(1):395
- CONCLUSIONS: Using systems biology approaches for the analysis of metabolomics and genetic data, we integrated several biological processes, which lead to findings that may functionally connect genetic variants with complex diseases.