Obesity-Related Glomerulopathy: A Latent Change in Obesity Requiring More Attention

Yang, Shuting; Cao, Chuqing; Deng, Tuo; Zhang, Zhou

doi:10.1159/000507784

Cited by 40 publications

(33 citation statements)

References 80 publications

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“…The increased sympathetic activation in obesity stimulates the renin-angiotensin system, resulting in insulin resistance (30). Insulin resistance resulting from insulin signaling interfering subsequently induces podocyte apoptosis, hypertrophy of the remaining podocytes, and glomerulosclerosis (31). In our study, reduced ADH1 was observed in genetically obese db/db mice.…”

Section: Discussionsupporting

confidence: 52%

Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression

Xie¹,

Guo²,

Lü³

et al. 2021

Ann Transl Med

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Background: Inositol-requiring enzyme 1 (IRE1) plays a critical role in attenuating endoplasmic reticulum (ER) stress associated with renal injury which may also be a factor in diabetic nephropathy (DN). Alcohol dehydrogenase type I (ADH1) activity is prominent in the kidney, ADH1 activity is also reported to exert protective effects against ER stress that are not caused by alcohol consumption. However, the role of IRE1 in DN and the correlation between IRE1 and ADH1 activity remain unclear.Methods: IRE1α floxed mice (Ire1 f/f ) of C57BL/6J background were established and crossbred with Ire1α f/f mice to produce podocyte-specific IRE1α knockout mice. Male db/db mice (C57BLKS/J-leprdb/ leprdb mice) were used as a DN model. Male mice were made diabetic by injection of streptozotocin. pLKO.1-based vectors encoding short hairpin RNA (shRNA) specific to the IRE1α gene were transfected into HEK293T cells to knockdown IRE1α in mouse podocytes. ELISA, Masson's staining, and electron microscopy were performed to analyze the development of DN. The ADH1 expression was assayed by qPCR and western blot.Results: We found that IRE activity was increased in the glomeruli of DN mouse models. In contrast, ADH1 expression was decreased in these models and mice with podocyte-specific disruption of IRE1 (PKO mice). PKO mice that were made diabetic using strepto zotocin exhibited accelerated proteinuria, enhanced glomerular fibrosis, and podocyte cell death. In addition, in cultured podocytes, the knockdown of IRE1 downregulated the ADH1 mRNA expression and induced ER stress, consistent with the result of PKO mice, while its detrimental effects were reversed by ADH1 overexpression.Conclusions: Activation of IRE1 in podocytes serves to limit the progress of DN. The dependence of kidney ADH1 expression on podocyte IRE1 further suggests that ADH1 activity may play an important role downstream of IRE1 in protecting against DN.

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Section: Discussionsupporting

confidence: 52%

Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression

Xie¹,

Guo²,

Lü³

et al. 2021

Ann Transl Med

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“…While TNF-alpha plays a fundamental role in progression of renal fibrosis, the increase in intracellular lipids has a nephrotoxic effect (culminating in glomerulosclerosis), compromising the structure and functioning of mitochondria, which contributes to progression of kidney disease. 87 Increased insulin production and insulin resistance contribute to mesangial expansion and renal fibrosis, and the observed activation of the renin-angiotensin-aldosterone system, since the vasoconstrictor effect of angiotensin II on renal arterioles leads to increased production of endothelin-1, stimulating proliferation of mesangial matrix, sodium retention, and vasoconstriction of renal arterioles. 88 Coronavirus can cause acute kidney damage in up to 15% of cases, which contributes to mortality.…”

Section: Pathophysiology Of Obesity and Its Relationship With Covid-1mentioning

confidence: 99%

COVID-19 and obesity in childhood and adolescence: a clinical review

Nogueira‐de‐Almeida

Ciampo

Ferraz

et al. 2020

Jornal de Pediatria

177

136

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Objective To identify factors that contribute to the increased susceptibility and severity of COVID-19 in obese children and adolescents, and its health consequences. Sources Studies published between 2000 and 2020 in the PubMed, MEDLINE, Scopus, SciELO, and Cochrane databases. Summary of findings Obesity is a highly prevalent comorbidity in severe cases of COVID-19 in children and adolescents; social isolation may lead to increase fat accumulation. Excessive adipose tissue, deficit in lean mass, insulin resistance, dyslipidemia, hypertension, high levels of proinflammatory cytokines, and low intake of essential nutrients are factors that compromise the functioning of organs and systems in obese individuals. These factors are associated with damage to immune, cardiovascular, respiratory, and urinary systems, along with modification of the intestinal microbiota (dysbiosis). In severe acute respiratory syndrome coronavirus 2 infection, these organic changes from obesity may increase the need for ventilatory assistance, risk of thromboembolism, reduced glomerular filtration rate, changes in the innate and adaptive immune response, and perpetuation of the chronic inflammatory response. Conclusions The need for social isolation can have the effect of causing or worsening obesity and its comorbidities, and pediatricians need to be aware of this issue. Facing children with suspected or confirmed COVID-19, health professionals should 1) diagnose excess weight; 2) advise on health care in times of isolation; 3) screen for comorbidities, ensuring that treatment is not interrupted; 4) measure levels of immunonutrients; 5) guide the family in understanding the specifics of the situation; and 6) refer to units qualified to care for obese children and adolescents when necessary.

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“…The limited presence of full nephrotic syndrome in patients with ORG can be clinically significant since a progressive increase in proteinuria may go unnoticed for years, leading to late diagnosis of renal failure (29) . Many studies suggest that obesity-associated insulin resistance increases the risk of CKD progression following a period of "silent" glomerular hyperfiltration (31,32) . Obesity is significantly related to the development and progression of renal diseases other than ORG (29, A c c e p t e d A r t i c l e [33][34][35][36][37][38] .…”

Section: The Adverse Effects Of Obesity On Renal Outcomesmentioning

confidence: 99%

Obesity and chronic kidney disease: prevalence, mechanism, and management

Yim

Yoo

2021

Clin Exp Pediatr

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The prevalence of childhood obesity is increasing worldwide at an alarming rate. While obesity is known to increase a variety of cardiovascular and metabolic diseases, it also acts as a risk factor for the development and progression of chronic kidney disease (CKD).During childhood and adolescence, severe obesity is associated with an increased prevalence and incidence of the early stages of kidney disease. Importantly, children born to obese mothers are also at increased risk of developing obesity and CKD later in life. The potential mechanisms underlying the association between obesity and CKD include hemodynamic factors, metabolic effects, and lipid nephrotoxicity. Weight reduction via increased physical activity, caloric restriction, treatment with angiotensin-converting enzyme inhibitors, and judicious bariatric surgery can be used to control obesity and obesity-related kidney disease.Preventive strategies to halt the obesity epidemic in the healthcare community are needed to reduce the widespread deleterious consequences of obesity including CKD development and progression.

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Obesity-Related Glomerulopathy: A Latent Change in Obesity Requiring More Attention

Cited by 40 publications

References 80 publications

Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression

Diabetic nephropathy in mice is aggravated by the absence of podocyte IRE1 and is correlated with reduced kidney ADH1 expression

COVID-19 and obesity in childhood and adolescence: a clinical review

Obesity and chronic kidney disease: prevalence, mechanism, and management

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