Role of Altered Renal Lipid Metabolism in the Development of Renal Injury Induced by a High-Fat Diet

Kume, Shinji; Uzu, Takashi; Araki, Shin‐ichi; Sugimoto, Toshiro; Isshiki, Keiji; Chin‐Kanasaki, Masami; Sakaguchi, Minoru; Kubota, Naoto; Terauchi, Yasuo; Kadowaki, Takashi; Haneda, Masakazu; Kashiwagi, Atsunori; Koya, Daisuke

doi:10.1681/asn.2007010089

Cited by 236 publications

(222 citation statements)

References 36 publications

(28 reference statements)

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“…AMPK activation by metformin restored the normal structure and physiology of kidney. Inhibition of AMPK has been reported to be associated with increased profibrotic markers (40). The decreased level of the phosphorylated form of AMPK coincided with increased collagen and extracellular matrix deposition in kidney of HFD-fed animals and its reversal by metformin treatment.…”

Section: Discussionmentioning

confidence: 89%

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Tikoo

Sharma

Amara

et al. 2016

Journal of Biological Chemistry

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Section: Discussionmentioning

confidence: 89%

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Tikoo

Sharma

Amara

et al. 2016

Journal of Biological Chemistry

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“…Whether upregulation of lipogenic enzymes and decreased amounts of lipolytic factors could imply direct lipotoxicity remains an area of active investigation. 34 Glomerulomegaly was observed in 100% of renal biopsies in a clinicopathologic study of obesity glomerulopathy. Despite the observed high incidence of glomerulomegaly, glomerular changes in obesity-induced renal injury are incomparable with those of diabetic nephropathy, mainly because of the lower severity of changes in the mesangial space.…”

Section: Structural Changes In the Kidneymentioning

confidence: 99%

Mechanisms of obesity-induced hypertension

et al. 2010

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The relationship between obesity and hypertension is well established both in children and adults. The mechanisms through which obesity directly causes hypertension are still an area of research. Activation of the sympathetic nervous system has been considered to have an important function in the pathogenesis of obesity-related hypertension. The arterial-pressure control mechanism of diuresis and natriuresis, according to the principle of infinite feedback gain, seems to be shifted toward higher blood-pressure levels in obese individuals. During the early phases of obesity, primary sodium retention exists as a result of increase in renal tubular reabsorption. Extracellular-fluid volume is expanded and the kidney-fluid apparatus is resetted to a hypertensive level, consistent with a model of hypertension because of volume overload. Plasma renin activity, angiotensinogen, angiotensin II and aldosterone values display significant increase during obesity. Insulin resistance and inflammation may promote an altered profile of vascular function and consequently hypertension. Leptin and other neuropeptides are possible links between obesity and the development of hypertension. Obesity should be considered as a chronic medical condition, which is likely to require long-term treatment. Understanding of the mechanisms associated with obesity-related hypertension is essential for successful treatment strategies. Hypertension Research (2010) 33, 386-393; doi:10.1038/hr.2010.9Keywords: leptin; obesity; pressure natriuresis; rennin-angiotensin-aldosterone system; sympathetic nervous system INTRODUCTION Obesity is a common disorder that develops from the interaction between the genotype and the environment and involves social, behavioral, cultural, physiological, metabolic and genetic factors. A large number of studies have shown that obesity has an important negative impact on health in a population, leading to the recommendation for general practitioners to have an important function in the management of this condition and of its associated comorbidities such as hypertension, hyperlipidemia and hyperinsulinemia/insulin resistance. The relationship between obesity and hypertension is well established both in adults and children. 1,2 Obese individuals exhibit higher levels of office as well as ambulatory blood pressure (BP) from childhood to old age. Obese subjects display higher BP levels than non-obese individuals even in the normotensive range. The combination of obesity, hypertension and other cardiovascular risk factors significantly increases the probability of adverse cardiovascular outcomes, and raises considerations for aggressive treatment strategies. 3 The mechanisms through which obesity directly causes hypertension are still an area of research. Human and animal studies have elucidated the function of adipose tissue derivatives (adipokines and cytokines), neurohumoral pathways, metabolic functions and modulation of pressor/depressor mechanisms. Although obesity-related hypertension may be the result of a combinatio...

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“…19 Mice were initially subjected to acclimation period of five cycles before blood pressure assessment. Subsequently, systolic blood pressure was measured in each mouse for 60 continuous cycles and an average of systolic blood pressure was quantified as previously described.…”

Section: Blood Pressure Monitoringmentioning

confidence: 99%

“…Subsequently, systolic blood pressure was measured in each mouse for 60 continuous cycles and an average of systolic blood pressure was quantified as previously described. 19 …”

Section: Blood Pressure Monitoringmentioning

confidence: 99%

Reduced Krüppel-Like Factor 2 Aggravates Glomerular Endothelial Cell Injury and Kidney Disease in Mice with Unilateral Nephrectomy

Zhong

Mallipattu

Estrada

et al. 2016

The American Journal of Pathology

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Loss of functional nephrons induces compensatory glomerular hyperfiltration and hypertrophy, leading to the progression of chronic kidney disease. Krüppel-like factor 2 (KLF2), a shear-stresseinducible transcription factor, confers protection against endothelial injury. Because glomerular hyperfiltration is associated with shear stress, we hypothesized that KLF2 may be an important factor in the compensatory response to unilateral nephrectomy (UNX). To test this hypothesis, endothelial cellespecific Klf2 heterozygous knockout mice (KO) and their wild-type littermate control (WT) underwent either UNX or sham-operation. WT-UNX mice developed compensatory renal hypertrophy as expected, whereas KO-UNX mice did not. KO-UNX mice exhibited higher blood pressure, reduced glomerular filtration rate, and significant increase in proteinuria and glomerulosclerosis compared to WT-UNX. Expression of endothelial nitric oxide synthase (official name Nos3), a known transcriptional target gene of KLF2, was significantly reduced and dysregulation of other endothelial genes was also observed in the glomeruli of KO-UNX when compared to WT-UNX and sham-operated mice. Furthermore, both podocyte number and expression of podocyte markers were also significantly reduced in KO-UNX glomeruli, indicating a potential cross talk between glomerular endothelial cells and podocytes. Finally, decreased renal expression of KLF2 in nephrectomy patients was associated with the progression of kidney disease. Taken together, our data demonstrate a protective role of KLF2 against glomerular endothelial cell injury and progression of chronic kidney disease in the model of compensatory renal hypertrophy.

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Role of Altered Renal Lipid Metabolism in the Development of Renal Injury Induced by a High-Fat Diet

Cited by 236 publications

References 36 publications

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Metformin Improves Metabolic Memory in High Fat Diet (HFD)-induced Renal Dysfunction

Mechanisms of obesity-induced hypertension

Reduced Krüppel-Like Factor 2 Aggravates Glomerular Endothelial Cell Injury and Kidney Disease in Mice with Unilateral Nephrectomy

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