scholarly journals Alterations in hepatic one-carbon metabolism and related pathways following a high-fat dietary intervention

2011 ◽  
Vol 43 (8) ◽  
pp. 408-416 ◽  
Author(s):  
Isabel Rubio-Aliaga ◽  
Baukje de Roos ◽  
Manuela Sailer ◽  
Gerard A. McLoughlin ◽  
Mark V. Boekschoten ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Carbon Metabolism ◽  
Dietary Intervention ◽  
Liver Steatosis ◽  
Oxidative Capacity ◽  
Blood Cholesterol ◽  
High Fat ◽  
One Carbon Metabolism ◽  
Fat Feeding

Obesity frequently leads to insulin resistance and the development of hepatic steatosis. To characterize the molecular changes that promote hepatic steatosis, transcriptomics, proteomics, and metabolomics technologies were applied to liver samples from C57BL/6J mice obtained from two independent intervention trials. After 12 wk of high-fat feeding the animals became obese, hyperglycemic, and insulin resistant, had elevated levels of blood cholesterol and VLDL, and developed hepatic steatosis. Nutrigenomic analysis revealed alterations of key metabolites and enzyme transcript levels of hepatic one-carbon metabolism and related pathways. The hepatic oxidative capacity and the lipid milieu were significantly altered, which may play a key role in the development of insulin resistance. Additionally, high choline levels were observed after the high-fat diet. Previous studies have linked choline levels with insulin resistance and hepatic steatosis in conjunction with changes of certain metabolites and enzyme levels of one-carbon metabolism. The present results suggest that the coupling of high levels of choline and low levels of methionine plays an important role in the development of insulin resistance and liver steatosis. In conclusion, the complexities of the alterations induced by high-fat feeding are multifactorial, indicating that the interplay between several metabolic pathways is responsible for the pathological consequences.

Black rice anthocyanins alleviate hyperlipidemia, liver steatosis and insulin resistance by regulating lipid metabolism and gut microbiota in obese mice

2021 ◽  
Author(s):  
Haizhao Song ◽  
Xinchun Shen ◽  
Yang Zhou ◽  
Xiaodong Zheng
Keyword(s):  
Insulin Resistance ◽  
Lipid Metabolism ◽  
Gut Microbiota ◽  
Hepatic Steatosis ◽  
High Fat Diet ◽  
Liver Steatosis ◽  
Obese Mice ◽  
Black Rice ◽  
High Fat ◽  
Diet Induced Obesity

Supplementation of black rice anthocyanins (BRAN) alleviated high fat diet-induced obesity, insulin resistance and hepatic steatosis by improvement of lipid metabolism and modification of the gut microbiota.

scholarly journals Mice lacking NOX2 are hyperphagic and store fat preferentially in the liver

2014 ◽  
Vol 306 (12) ◽  
pp. E1341-E1353 ◽  
Author(s):  
Sheila R. Costford ◽  
Jason Castro-Alves ◽  
Kenny L. Chan ◽  
Liane J. Bailey ◽  
Minna Woo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Immune Cells ◽  
Low Grade ◽  
High Fat ◽  
Insulin Resistant ◽  
Nadph Oxidase Complex ◽  
Low Grade Inflammation ◽  
Fat Feeding

Chronic low-grade inflammation is an important contributor to the development of insulin resistance, a hallmark of type 2 diabetes mellitus (T2DM). Obesity and high-fat feeding lead to infiltration of immune cells into metabolic tissues, promoting inflammation and insulin resistance. We hypothesized that macrophages from mice lacking NOX2 ( Cybb), an essential component of the NADPH oxidase complex highly expressed in immune cells and associated with their inflammatory response, would be less inflammatory and that these mice would be protected from the development of high-fat-induced insulin resistance. Bone marrow-derived macrophages from NOX2 knockout (NOX2-KO) mice expressed lower levels of inflammatory markers ( Nos2, Il6); however, NOX2-KO mice were hyperphagic and gained more weight than wild-type (WT) mice when fed either a chow or a high-fat (HF) diet. Surprisingly, NOX2-KO mice stored less lipid in epididymal white adipose tissue but more lipid in liver and had higher indexes of liver inflammation and macrophage infiltration than WT mice. Contrary to our hypothesis, HF-fed NOX2-KO mice were hyperinsulinemic and more insulin resistant than HF-fed WT mice, likely as a result of their higher hepatic steatosis and inflammation. In summary, NOX2 depletion promoted hyperphagia, hepatic steatosis, and inflammation with either normal or high-fat feeding, exacerbating insulin resistance. We propose that NOX2 participates in food intake control and lipid distribution in mice.

scholarly journals Effect of a Tailored Dietary Intervention with High or Standard Protein Intake on B-Vitamin and One Carbon Metabolism Status in Healthy Older Males: A 10 Week Randomised Controlled Trial

Proceedings ◽  
2019 ◽  
Vol 8 (1) ◽  
pp. 19
Author(s):  
Nicola Gillies ◽  
Amber M. Milan ◽  
Pankaja Sharma ◽  
Brenan Durainayagam ◽  
Sarah M. Mitchell ◽  
...  
Keyword(s):  
Randomised Controlled Trial ◽  
Carbon Metabolism ◽  
Protein Intake ◽  
Dietary Intervention ◽  
Controlled Trial ◽  
One Carbon Metabolism ◽  
Randomised Controlled ◽  
B Vitamin ◽  
Standard Protein ◽  
Older Males

Background: Maintaining optimal status of folate and metabolically [...]

High-fat Feeding Causes Inflammation and Insulin Resistance in the Ventral Tegmental Area in Mice

Neuroscience ◽  
2021 ◽  
Vol 461 ◽  
pp. 72-79
Author(s):  
Akira Mizoguchi ◽  
Ryoichi Banno ◽  
Runan Sun ◽  
Hiroshi Yaginuma ◽  
Keigo Taki ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Ventral Tegmental Area ◽  
High Fat ◽  
Ventral Tegmental ◽  
Fat Feeding

scholarly journals Na+-sensitive elevation in blood pressure is ENaC independent in diet-induced obesity and insulin resistance

2016 ◽  
Vol 310 (9) ◽  
pp. F812-F820 ◽  
Author(s):  
Jonathan M. Nizar ◽  
Wuxing Dong ◽  
Robert B. McClellan ◽  
Mariana Labarca ◽  
Yuehan Zhou ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Blood Pressure ◽  
Metabolic Syndrome ◽  
Elevated Blood Pressure ◽  
Elevated Blood ◽  
High Fat ◽  
Electrolyte Excretion ◽  
Diet Induced Obesity ◽  
Collecting Ducts ◽  
Fat Feeding

The majority of patients with obesity, insulin resistance, and metabolic syndrome have hypertension, but the mechanisms of hypertension are poorly understood. In these patients, impaired sodium excretion is critical for the genesis of Na+-sensitive hypertension, and prior studies have proposed a role for the epithelial Na+ channel (ENaC) in this syndrome. We characterized high fat-fed mice as a model in which to study the contribution of ENaC-mediated Na+ reabsorption in obesity and insulin resistance. High fat-fed mice demonstrated impaired Na+ excretion and elevated blood pressure, which was significantly higher on a high-Na+ diet compared with low fat-fed control mice. However, high fat-fed mice had no increase in ENaC activity as measured by Na+ transport across microperfused cortical collecting ducts, electrolyte excretion, or blood pressure. In addition, we found no difference in endogenous urinary aldosterone excretion between groups on a normal or high-Na+ diet. High fat-fed mice provide a model of metabolic syndrome, recapitulating obesity, insulin resistance, impaired natriuresis, and a Na+-sensitive elevation in blood pressure. Surprisingly, in contrast to previous studies, our data demonstrate that high fat feeding of mice impairs natriuresis and produces elevated blood pressure that is independent of ENaC activity and likely caused by increased Na+ reabsorption upstream of the aldosterone-sensitive distal nephron.

Abstract 67: Intervention With Citrus Flavonoids Reverses Existing Metabolic Disorders and Attenuates the Progression of Advanced Atherosclerosis in High Fat--Fed LDLr-/- Mice

2014 ◽  
Vol 34 (suppl_1) ◽  
Author(s):  
Amy C Burke ◽  
Brian G Sutherland ◽  
Cynthia G Sawyez ◽  
Dawn E Telford ◽  
Joseph Umoh ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Hepatic Steatosis ◽  
Caloric Intake ◽  
Atherosclerotic Lesion ◽  
Lesion Size ◽  
High Fat ◽  
Rapid Weight Gain ◽  
Metabolic Dysregulation ◽  
The Metabolic Syndrome ◽  
Citrus Flavonoids

Previous studies demonstrated that addition of the citrus flavonoids naringenin or nobiletin to a high-fat diet prevented the development of many disorders linked to the metabolic syndrome. In the present study, we assessed the ability of intervention with nobiletin or naringenin to reverse pre-established obesity, insulin resistance, hepatic steatosis, dyslipidemia and attenuate atherogenesis. Ldlr-/- mice were fed chow or a high-fat, cholesterol-containing (HFHC) diet for 12 weeks. For an additional 12 weeks, the HFHC-fed mice: (1) continued on the HFHC diet or were transferred to (2) chow, (3) HFHC + 3% naringenin, or (4) HFHC + 0.3% nobiletin. Following rapid weight gain during HFHC-induction, intervention with naringenin or nobiletin stimulated weight loss, while maintaining caloric intake. Micro-CT imaging revealed flavonoid intervention reversed adipose tissue accumulation by 40-60% in both subcutaneous and visceral depots. At 12 weeks, the HFHC-fed mice were hyperinsulinemic (6-fold), which was accompanied by increased fasting plasma glucose. Intervention with either flavonoid normalized plasma insulin and glucose and corrected impaired insulin and glucose tolerance. The HFHC diet increased cholesterol within VLDL (10-fold) and LDL (6-fold), which was reduced (~50%) by either naringenin or nobiletin intervention. HFHC-induction significantly increased hepatic steatosis. Flavonoid intervention reduced hepatic cholesterol (>50%) and triglyceride (~20%) via increased expression of Pgc1a and Cpt1a and reduced expression of Srebp1c. HFHC-induction increased atherosclerotic lesion area (13-fold), which was increased a further 2.5-fold at 24 weeks. Flavonoid intervention modestly retarded lesion size progression (16-20%). As well, intervention with naringenin or nobiletin slowed the accumulation of aortic cholesterol (~30-45%) and reduced lesional necrotic area (~25%), suggesting improved lesion morphology. These studies demonstrate in mice with pre-existing metabolic dysregulation and atherosclerosis that intervention with naringenin or nobiletin reverses obesity, dyslipidemia, hepatic steatosis and insulin resistance, and modestly attenuates the progression of advanced atherosclerosis.

scholarly journals Hepatic Mitogen-Activated Protein Kinase Phosphatase 1 Selectively Regulates Glucose Metabolism and Energy Homeostasis

2014 ◽  
Vol 35 (1) ◽  
pp. 26-40 ◽  
Author(s):  
Ahmed Lawan ◽  
Lei Zhang ◽  
Florian Gatzke ◽  
Kisuk Min ◽  
Michael J. Jurczak ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Protein Kinase ◽  
Glucose Metabolism ◽  
Energy Homeostasis ◽  
Mitogen Activated Protein Kinase ◽  
Hepatic Insulin Resistance ◽  
Fibroblast Growth Factor 21 ◽  
High Fat ◽  
Mitogen Activated Protein ◽  
Fat Feeding

The liver plays a critical role in glucose metabolism and communicates with peripheral tissues to maintain energy homeostasis. Obesity and insulin resistance are highly associated with nonalcoholic fatty liver disease (NAFLD). However, the precise molecular details of NAFLD remain incomplete. The p38 mitogen-activated protein kinase (MAPK) and c-Jun NH2-terminal kinase (JNK) regulate liver metabolism. However, the physiological contribution of MAPK phosphatase 1 (MKP-1) as a nuclear antagonist of both p38 MAPK and JNK in the liver is unknown. Here we show that hepatic MKP-1 becomes overexpressed following high-fat feeding. Liver-specific deletion of MKP-1 enhances gluconeogenesis and causes hepatic insulin resistance in chow-fed mice while selectively conferring protection from hepatosteatosis upon high-fat feeding. Further, hepatic MKP-1 regulates both interleukin-6 (IL-6) and fibroblast growth factor 21 (FGF21). Mice lacking hepatic MKP-1 exhibit reduced circulating IL-6 and FGF21 levels that were associated with impaired skeletal muscle mitochondrial oxidation and susceptibility to diet-induced obesity. Hence, hepatic MKP-1 serves as a selective regulator of MAPK-dependent signals that contributes to the maintenance of glucose homeostasis and peripheral tissue energy balance. These results also demonstrate that hepatic MKP-1 overexpression in obesity is causally linked to the promotion of hepatosteatosis.

scholarly journals Effect of the Hepatocyte-Specific Deletion of SND1 in Mice on the Liver Insulin Resistance and Acute Liver Failure

2020 ◽  
Author(s):  
Chunyan Zhao ◽  
Xiaoteng Cui ◽  
Baoxin Qian ◽  
Nan Zhang ◽  
Lingbiao Xin ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Liver Failure ◽  
Acute Liver Failure ◽  
Cholesterol Level ◽  
Hepatic Steatosis ◽  
Glucose Homeostasis ◽  
Hepatic Failure ◽  
High Fat Diet ◽  
High Fat ◽  
Specific Deletion

Abstract Background: The multifunctional protein SND1 was reported to be involved in a variety of biological processes, such as cell cycle, proliferation or lipogenesis. We previously proposed that global-expressed SND1 in vivo is likely to be a key regulator for ameliorating HFD-induced hepatic steatosis and systemic insulin resistance. Herein, we are very interested in investigating further whether the hepatocyte-specific deletion of SND1 affects the insulin resistance or acute liver failure (ALF) of mice.Methods: By using Cre-loxP technique, we constructed conditional knockout (LKO) mice of SND1 driven by albumin in hepatocytes and analyze the changes of glucose homeostasis, cholesterol level, hepatic steatosis and hepatic failure under the treatment of high-fat diet (HFD) or upon the simulation of Lipopolysaccharide/galactosamine (LPS/GalN).Results: No difference for the body weight, liver weight, and cholesterol level was detected. Furthermore, we did not observe the alteration of glucose homeostasis in SND1 hepatic knockout mice on either chow diet or high-fat diet. Besides, hepatocyte-specific deletion of SND1 failed to influence the hepatic failure of mice induced by LPS/GalN.Conclusions: These findings suggest that hepatic SND1, independently, is insufficient for changing glucose homeostasis, hepatic lipid accumulation and inflammation. The synergistic action of multiple organs may contribute to the role of SND1 in insulin sensitivity or inflammatory response.

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