scholarly journals Maternal obesity increases the risk of metabolic disease and impacts renal health in offspring

2018 ◽  
Vol 38 (2) ◽  
Author(s):  
Sarah J. Glastras ◽  
Hui Chen ◽  
Carol A. Pollock ◽  
Sonia Saad
Keyword(s):  
Metabolic Disease ◽  
Kidney Disease ◽  
Maternal Obesity ◽  
Disease Risk ◽  
Reproductive Age ◽  
Intrauterine Environment ◽  
Alcoholic Fatty Liver ◽  
Increased Risk ◽  
Epigenetic Modulation

Obesity, together with insulin resistance, promotes multiple metabolic abnormalities and is strongly associated with an increased risk of chronic disease including type 2 diabetes (T2D), hypertension, cardiovascular disease, non-alcoholic fatty liver disease (NAFLD) and chronic kidney disease (CKD). The incidence of obesity continues to rise in astronomical proportions throughout the world and affects all the different stages of the lifespan. Importantly, the proportion of women of reproductive age who are overweight or obese is increasing at an alarming rate and has potential ramifications for offspring health and disease risk. Evidence suggests a strong link between the intrauterine environment and disease programming. The current review will describe the importance of the intrauterine environment in the development of metabolic disease, including kidney disease. It will detail the known mechanisms of fetal programming, including the role of epigenetic modulation. The evidence for the role of maternal obesity in the developmental programming of CKD is derived mostly from our rodent models which will be described. The clinical implication of such findings will also be discussed.

Abstract MP74: Long Term Risk-Factor Profiles for Chronic Kidney Disease in the Framingham Heart Study

Circulation ◽  
2013 ◽  
Vol 127 (suppl_12) ◽  
Author(s):  
Gearoid M McMahon ◽  
Sarah R Preis ◽  
Shih-Jen Hwang ◽  
Caroline S Fox
Keyword(s):  
Risk Factors ◽  
Chronic Kidney Disease ◽  
Risk Factor ◽  
Kidney Disease ◽  
Framingham Heart Study ◽  
Disease Risk ◽  
Cardiovascular Disease Risk ◽  
Standard Deviation Increase ◽  
Heart Study ◽  
Increased Risk

Background: Chronic Kidney Disease (CKD) is an important public health issue and is associated with an increased risk of cardiovascular disease. Risk factors for CKD are well established, but most are typically assessed at or near the time of CKD diagnosis. Our hypothesis was that risk factors for CKD are present earlier in the course of the disease. We compared the prevalence of risk factors between CKD cases and controls at time points up to 30 years prior to CKD diagnosis. Methods: Participants were drawn from the Framingham Heart Study Offspring cohort. CKD was defined as an estimated glomerular filtration rate of ≤60ml/min/1.73m2. Incident CKD cases occurring at examination cycles 6, 7, and 8 were age- and sex-matched 1:2 to controls. Risk factors including systolic blood pressure (SBP), hypertension, lipids, diabetes, smoking status, body mass index (BMI) and dipstick proteinuria were measured at the time of CKD diagnosis and 10, 20 and 30 years prior. Logistic regression models, adjusted for age, sex, and time period, were constructed to compare risk factor profiles at each time point between cases and controls Results: During follow-up, 441 new cases of CKD were identified and these were matched to 882 controls (mean age 69.2 years, 52.4% women). Up to 30 years prior to CKD diagnosis, those who ultimately developed CKD were more likely to have hypertension (OR 1.74, CI 1.21-2.49), be obese (OR 1.74, CI 1.15-2.63) and have higher triglycerides (OR 1.43, CI 1.12-1.84, p=0.005 per 1 standard deviation increase). Each 10mmHg increase in SBP was associated with an OR of 1.22 for future CKD (95% CI 1.10-1.35) Additionally, cases were more likely to have diabetes (OR 2.90, CI 1.59-5.29) and be on antihypertensive therapy (OR 1.65, CI 1.14-2.40, p=0.009) up to 20 years prior to diagnosis. Increasing HDLc was associated with a lower risk of CKD (OR 0.84, CI 0.81-0.97 per 10mg/dl). Conclusions: As many as 30 years prior to diagnosis, risk factors for CKD are identifiable. In particular, modifiable risk factors such as obesity, hypertension and dyslipidemia are present early in the course of the disease. These findings demonstrate the importance of early identification of risk factors in patients at risk of CKD through a life-course approach.

Obesity and oocyte quality: Significant implications for ART and Emerging mechanistic insights

2021 ◽  
Author(s):  
Macarena B Gonzalez ◽  
Rebecca L Robker ◽  
Ryan D Rose
Keyword(s):  
Pregnancy Complications ◽  
Maternal Obesity ◽  
Ovarian Function ◽  
Polycystic Ovary ◽  
Live Birth Rate ◽  
Oocyte Quality ◽  
Reproductive Age ◽  
Developmental Competence ◽  
Obese Women ◽  
Increased Risk

Abstract The prevalence of obesity in adults worldwide, and specifically in women of reproductive age, is concerning given the risks to fertility posed by the increased risk of type 2 diabetes, metabolic syndrome and other non-communicable diseases. Obesity has a multi-systemic impact in female physiology that is characterized by the presence of oxidative stress, lipotoxicity, and the activation of pro-inflammatory pathways, inducing tissue-specific insulin resistance and ultimately conducive to abnormal ovarian function. A higher body mass is linked to Polycystic Ovary Syndrome, dysregulated menstrual cycles, anovulation, and longer time to pregnancy, even in ovulatory women. In the context of ART, compared to women of normal BMI, obese women have worse outcomes in every step of their journey, resulting in reduced success measured as live birth rate. Even after pregnancy is achieved, obese women have a higher chance of miscarriage, gestational diabetes, pregnancy complications, birth defects, and most worryingly, a higher risk of stillbirth and neonatal death. The potential for compounding effects of ART on pregnancy complications and infant morbidities in obese women has not been studied. There is still much debate in the field on whether these poorer outcomes are mainly driven by defects in oocyte quality, abnormal embryo development or an unaccommodating uterine environment, however the clinical evidence to date suggests a combination of all three are responsible. Animal models of maternal obesity shed light on the mechanisms underlaying the effects of obesity on the peri-conception environment, with recent findings pointing to lipotoxicity in the ovarian environment as a key driver of defects in oocytes that have not only reduced developmental competence but long-lasting effects in offspring health.

Current aspects of the development and progression of fluoride-related chronic kidney disease

2021 ◽  
Vol 16 (3) ◽  
pp. 84-91
Author(s):  
N.S. Morozova ◽  
◽  
Ad.A. Mamedov ◽  
D.Yu. Lakomova ◽  
L.D. Maltseva ◽  
...  
Keyword(s):  
Chronic Kidney Disease ◽  
Molecular Markers ◽  
Kidney Disease ◽  
Disease Risk ◽  
Chemical Elements ◽  
Fluoride Concentration ◽  
Underlying Disease ◽  
Cochrane Library ◽  
Increased Risk ◽  
Asymptomatic Phase

Difficulties associated with the identification of a major risk factor for chronic kidney disease (CKD) (mainly in children without obvious anatomical causes), long-lasting asymptomatic phase, and irreversible kidney damage caused by chemical elements resulted in a particular interest to the problem of diagnosis and timely treatment of CKD. This review aims to summarize available information on the role of increased fluoride concentration in the development of CKD of uncertain etiology. We included more than 200 publications found in Scopus, Web of Science, Cochrane Library, and PubMed. We analyzed factors associated with an increased risk of fluoride-related CKD and identified possible mechanisms underlying disease progression. In addition to that, we proposed potential molecular markers to detect early stages of CKD. We described new promising therapeutic targets with the consideration of key elements of disease pathogenesis, poor prognosis, and age limits for existing nephroprotective drugs. Key words: fluoride, chronic kidney disease, risk factors, pathogenesis, molecular markers

scholarly journals Associations of Urine Biomarkers with Kidney Function Decline in HIV-Infected and Uninfected Men

2019 ◽  
Vol 50 (5) ◽  
pp. 401-410 ◽  
Author(s):  
Simon B. Ascher ◽  
Rebecca Scherzer ◽  
Michelle M. Estrella ◽  
Michael G. Shlipak ◽  
Derek K. Ng ◽  
...  
Keyword(s):  
Risk Factors ◽  
Kidney Disease ◽  
Kidney Function ◽  
Disease Risk ◽  
Kidney Injury ◽  
Procollagen Type ◽  
Urine Albumin ◽  
Urine Biomarkers ◽  
Increased Risk ◽  
Egfr Decline

Background: HIV-infected (HIV+) persons are at increased risk of chronic kidney disease, but serum creatinine does not detect early losses in kidney function. We hypothesized that urine biomarkers of kidney damage would be associated with subsequent changes in kidney function in a contemporary cohort of HIV+ and HIV-uninfected (HIV–) men. Methods: In the Multicenter AIDS Cohort Study, we measured baseline urine concentrations of 5 biomarkers from 2009 to 2011 in 860 HIV+ and 337 HIV– men: albumin, alpha-1-microglobulin (α1m), interleukin-18 (IL-18), kidney injury molecule-1 (KIM-1), and procollagen type III N-terminal propeptide (PIIINP). We evaluated associations of urine biomarker concentrations with annual changes in estimated glomerular filtration rate (eGFR) using multivariable linear mixed models adjusted for demographics, traditional kidney disease risk factors, HIV-related risk factors, and baseline eGFR. Results: Over a median follow-up of 4.8 years, the average annual eGFR decline was 1.42 mL/min/1.73 m2/year in HIV+ men and 1.22 mL/min/1.73 m2/year in HIV– men. Among HIV+ men, the highest vs. lowest tertiles of albumin (–1.78 mL/min/1.73 m2/year, 95% CI –3.47 to –0.09) and α1m (–2.43 mL/min/1.73 m2/year, 95% CI –4.14 to –0.73) were each associated with faster annual eGFR declines after multivariable adjustment. Among HIV– men, the highest vs. lowest tertile of α1m (–2.49 mL/min/1.73 m2/year, 95% CI –4.48 to –0.50) was independently associated with faster annual eGFR decline. Urine IL-18, KIM-1, and PIIINP showed no independent associations with eGFR decline, regardless of HIV serostatus. Conclusions: Among HIV+ men, higher urine albumin and α1m are associated with subsequent declines in kidney function, independent of eGFR.

scholarly journals Integrative genomics reveal a role for MCPIP1 in adipogenesis and adipocyte metabolism

2019 ◽  
Vol 77 (23) ◽  
pp. 4899-4919 ◽  
Author(s):  
Magdalena Losko ◽  
Dobrochna Dolicka ◽  
Natalia Pydyn ◽  
Urszula Jankowska ◽  
Sylwia Kedracka-Krok ◽  
...  
Keyword(s):  
Signal Transmission ◽  
Proteome Analysis ◽  
Mutant Form ◽  
Integrative Genomics ◽  
Rna Seq ◽  
Alcoholic Fatty Liver ◽  
Monocyte Chemoattractant Protein 1 ◽  
Increased Risk

AbstractObesity is considered a serious chronic disease, associated with an increased risk of developing cardiovascular diseases, non-alcoholic fatty liver disease and type 2 diabetes. Monocyte chemoattractant protein-1-induced protein-1 (MCPIP1) is an RNase decreasing stability of transcripts coding for inflammation-related proteins. In addition, MCPIP1 plays an important role in the regulation of adipogenesis in vitro by reducing the expression of key transcription factors, including C/EBPβ. To elucidate the role of MCPIP1 in adipocyte biology, we performed RNA-Seq and proteome analysis in 3T3-L1 adipocytes overexpressing wild-type (WTMCPIP1) and the mutant form of MCPIP1 protein (D141NMCPIP1). Our RNA-Seq analysis followed by confirmatory Q-RT-PCR revealed that elevated MCPIP1 levels in 3T3-L1 adipocytes upregulated transcripts encoding proteins involved in signal transmission and cellular remodeling and downregulated transcripts of factors involved in metabolism. These data are consistent with our proteomic analysis, which showed that MCPIP1 expressing adipocytes exhibit upregulation of proteins involved in cellular organization and movement and decreased levels of proteins involved in lipid and carbohydrate metabolism. Moreover, MCPIP1 adipocytes are characterized by decreased level of insulin receptor, reduced insulin-induced Akt phosphorylation, as well as depleted Glut4 level and impaired glucose uptake. Overexpression of Glut4 in 3T3-L1 cells expressed WTMCPIP1 rescued adipogenesis. Interestingly, we found decreased level of MCPIP1 along with an increase in body mass index in subcutaneous adipose tissue. The presented data show a novel role of MCPIP1 in modulating insulin sensitivity in adipocytes. Overall, our findings demonstrate that MCPIP1 is an important regulator of adipogenesis and adipocyte metabolism.

scholarly journals Variation inAPOL1Contributes to Ancestry-Level Differences in HDLc-Kidney Function Association

2012 ◽  
Vol 2012 ◽  
pp. 1-10 ◽  
Author(s):  
Amy Rebecca Bentley ◽  
Ayo P. Doumatey ◽  
Guanjie Chen ◽  
Hanxia Huang ◽  
Jie Zhou ◽  
...  
Keyword(s):  
African Americans ◽  
Kidney Disease ◽  
Disease Risk ◽  
African Ancestry ◽  
Gene Encoding ◽  
Risk Variant ◽  
European Americans ◽  
Nationally Representative ◽  
High Density Cholesterol

Low levels of high-density cholesterol (HDLc) accompany chronic kidney disease, but the association between HDLc and the estimated glomerular filtration rate (eGFR) in the general population is unclear. We investigated the HDLc-eGFR association in nondiabetic Han Chinese (HC,n=1100), West Africans (WA,n=1497), and African Americans (AA,n=1539). There were significant differences by ancestry: HDLc was positively associated with eGFR in HC (β=0.13,P<0.0001), but negatively associated among African ancestry populations (WA: −0.19,P<0.0001; AA: −0.09,P=0.02). These differences were also seen in nationally-representative NHANES data (among European Americans: 0.09,P=0.005; among African Americans −0.14,P=0.03). To further explore the findings in African ancestry populations, we investigated the role of an African ancestry-specific nephropathy risk variant, rs73885319, in the gene encoding HDL-associated APOL1. Among AA, an inverse HDLc-eGFR association was observed only with the risk genotype (−0.38 versus 0.001;P=0.03). This interaction was not seen in WA. In summary, counter to expectation, an inverse HDLc-eGFR association was observed among those of African ancestry. Given theAPOL1× HDLc interaction among AA, genetic factors may contribute to this paradoxical association. Notably, these findings suggest that the unexplained mechanism by whichAPOL1affects kidney-disease risk may involve HDLc.

scholarly journals Variations in Adipokine GenesAdipoQ,Lep, andLepRAre Associated with Risk for Obesity-Related Metabolic Disease: The Modulatory Role of Gene-Nutrient Interactions

2011 ◽  
Vol 2011 ◽  
pp. 1-17 ◽  
Author(s):  
Jennifer Emily Enns ◽  
Carla G. Taylor ◽  
Peter Zahradka
Keyword(s):  
Metabolic Disease ◽  
Energy Homeostasis ◽  
Leptin Receptor ◽  
Disease Risk ◽  
Critical Role ◽  
Nucleotide Polymorphisms ◽  
Nutrient Interactions ◽  
The Metabolic Syndrome ◽  
Susceptible Populations

Obesity rates are rapidly increasing worldwide and facilitate the development of many related disease states, such as cardiovascular disease, the metabolic syndrome, type 2 diabetes mellitus, and various types of cancer. Variation in metabolically important genes can have a great impact on a population's susceptibility to becoming obese and/or developing related complications. The adipokines adiponectin and leptin, as well as the leptin receptor, are major players in the regulation of body energy homeostasis and fat storage. This paper summarizes the findings of single nucleotide polymorphisms in these three genes and their effect on obesity and metabolic disease risk. Additionally, studies of gene-nutrient interactions involving adiponectin, leptin, and the leptin receptor are highlighted to emphasize the critical role of diet in susceptible populations.

scholarly journals Recruitment of APOL1 kidney disease risk variants to lipid droplets attenuates cell toxicity

2019 ◽  
Vol 116 (9) ◽  
pp. 3712-3721 ◽  
Author(s):  
Justin Chun ◽  
Jia-Yue Zhang ◽  
Maris S. Wilkins ◽  
Balajikarthick Subramanian ◽  
Cristian Riella ◽  
...  
Keyword(s):  
Cell Death ◽  
Kidney Disease ◽  
Lipid Droplets ◽  
Disease Risk ◽  
Significant Proportion ◽  
Autophagic Flux ◽  
Cell Toxicity ◽  
Risk Variant ◽  
Risk Variants ◽  
Increased Risk

Two coding variants in the apolipoprotein L1 (APOL1) gene (termed G1 and G2) are strongly associated with increased risk of nondiabetic kidney disease in people of recent African ancestry. The mechanisms by which the risk variants cause kidney damage, although not well-understood, are believed to involve injury to glomerular podocytes. The intracellular localization and function of APOL1 in podocytes remain unclear, with recent studies suggesting possible roles in the endoplasmic reticulum (ER), mitochondria, endosomes, lysosomes, and autophagosomes. Here, we demonstrate that APOL1 also localizes to intracellular lipid droplets (LDs). While a large fraction of risk variant APOL1 (G1 and G2) localizes to the ER, a significant proportion of wild-type APOL1 (G0) localizes to LDs. APOL1 transiently interacts with numerous organelles, including the ER, mitochondria, and endosomes. Treatment of cells that promote LD formation with oleic acid shifted the localization of G1 and G2 from the ER to LDs, with accompanying reduction of autophagic flux and cytotoxicity. Coexpression of G0 APOL1 with risk variant APOL1 enabled recruitment of G1 and G2 from the ER to LDs, accompanied by reduced cell death. The ability of G0 APOL1 to recruit risk variant APOL1 to LDs may help explain the recessive pattern of kidney disease inheritance. These studies establish APOL1 as a bona fide LD-associated protein, and reveal that recruitment of risk variant APOL1 to LDs reduces cell toxicity, autophagic flux, and cell death. Thus, interventions that divert APOL1 risk variants to LDs may serve as a novel therapeutic strategy to alleviate their cytotoxic effects.

scholarly journals Metabolic programming in early life in humans

2019 ◽  
Vol 374 (1770) ◽  
pp. 20180123 ◽  
Author(s):  
Caroline H. D. Fall ◽  
Kalyanaraman Kumaran
Keyword(s):  
Metabolic Disease ◽  
Birth Weight ◽  
Early Life ◽  
Disease Risk ◽  
Evolutionary Medicine ◽  
Metabolic Effects ◽  
High Birth Weight ◽  
Preventive Strategy ◽  
Increased Risk

An association of low birth weight with an increased risk of adult cardiovascular disease and diabetes led to the developmental origins of health and disease (DOHaD) hypothesis, which proposes that undernutrition during early development permanently ‘programmes’ organ structure and metabolism, leading to vulnerability to later cardio-metabolic disease. High birth weight caused by maternal gestational diabetes is also associated with later diabetes, suggesting that fetal over-nutrition also has programming effects. Post-natal factors (excess weight gain/obesity, smoking, poor diets and physical inactivity) interact with fetal exposures to increase disease risk. Animal studies have shown permanent metabolic effects in offspring after alterations to maternal or early post-natal diets but evidence in humans is largely limited to observational and quasi-experimental situations such as maternal famine exposure. Randomized trials of maternal nutritional interventions during pregnancy have so far had limited follow-up of the offspring. Moreover, interventions usually started after the first trimester and therefore missed key peri-conceptional or early pregnancy events such as epigenetic changes, placentation and fetal organogenesis. Recent and ongoing trials intervening pre-conceptionally and powered for long-term offspring follow-up will address these issues. While current preventive strategies for cardio-metabolic disease focus on high-risk individuals in mid-life, DOHaD concepts offer a ‘primordial’ preventive strategy to reduce disease in future generations by improving fetal and infant development. This article is part of the theme issue ‘Developing differences: early-life effects and evolutionary medicine’.

Sign in / Sign up

Export Citation Format

Share Document