The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet

There is no author summary for this article yet. Authors can add summaries to their articles on ScienceOpen to make them more accessible to a non-specialist audience.

Abstract

Aims/Hypothesis

Developmental programming induced by maternal obesity influences the development of chronic disease in offspring. In the present study, we aimed to determine whether maternal obesity exaggerates obesity-related kidney disease.

Methods

Female C57BL/6 mice were fed high-fat diet (HFD) for six weeks prior to mating, during gestation and lactation. Male offspring were weaned to normal chow or HFD. At postnatal Week 8, HFD-fed offspring were administered one dose streptozotocin (STZ, 100 mg/kg i.p.) or vehicle control. Metabolic parameters and renal functional and structural changes were observed at postnatal Week 32.

Results

HFD-fed offspring had increased adiposity, glucose intolerance and hyperlipidaemia, associated with increased albuminuria and serum creatinine levels. Their kidneys displayed structural changes with increased levels of fibrotic, inflammatory and oxidative stress markers. STZ administration did not potentiate the renal effects of HFD. Though maternal obesity had a sustained effect on serum creatinine and oxidative stress markers in lean offspring, the renal consequences of maternal obesity were overwhelmed by the powerful effect of diet-induced obesity.

Conclusion

Maternal obesity portends significant risks for metabolic and renal health in adult offspring. However, diet-induced obesity is an overwhelming and potent stimulus for the development of CKD that is not potentiated by maternal obesity.

Related collections

Most cited references 28

Record: found
Abstract: found
Article: not found

Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood.

Abigail Fraser, Kate Tilling, Corrie Macdonald-Wallis … (2010)

We sought to examine the association of gestational weight gain (GWG) and prepregnancy weight with offspring adiposity and cardiovascular risk factors. Data from 5154 (for adiposity and blood pressure) and 3457 (for blood assays) mother-offspring pairs from a UK prospective pregnancy cohort were used. Random-effects multilevel models were used to assess incremental GWG (median and range of repeat weight measures per woman: 10 [1, 17]). Women who exceeded the 2009 Institute of Medicine-recommended GWG were more likely to have offspring with greater body mass index, waist, fat mass, leptin, systolic blood pressure, C-reactive protein, and interleukin-6 levels and lower high-density lipoprotein cholesterol and apolipoprotein A1 levels. Children of women who gained less than the recommended amounts had lower levels of adiposity, but other cardiovascular risk factors tended to be similar in this group to those of offspring of women gaining recommended amounts. When examined in more detail, greater prepregnancy weight was associated with greater offspring adiposity and more adverse cardiovascular risk factors at age 9 years. GWG in early pregnancy (0 to 14 weeks) was positively associated with offspring adiposity across the entire distribution but strengthened in women gaining >500 g/wk. By contrast, between 14 and 36 weeks, GWG was only associated with offspring adiposity in women gaining >500 g/wk. GWG between 14 and 36 weeks was positively and linearly associated with adverse lipid and inflammatory profiles, with these associations largely mediated by the associations with offspring adiposity. Greater maternal prepregnancy weight and GWG up to 36 weeks of gestation are associated with greater offspring adiposity and adverse cardiovascular risk factors. Before any GWG recommendations are implemented, the balance of risks and benefits of attempts to control GWG for short- and long-term outcomes in mother and child should be ascertained.

0 comments Cited 163 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: not found

Regulation of lipid accumulation by AMP-activated kinase [corrected] in high fat diet-induced kidney injury.

Anne-Emilie Declèves, Zarazuela Zolkipli, Joseph Satriano … (2014)

AMP-activated protein kinase (AMPK) is an important energy sensor that may be critical in regulating renal lipid accumulation. To evaluate the role of AMPK in mediating renal lipid accumulation, C57BL/6J mice were randomized to a standard diet, a high-fat diet, or a high-fat diet plus AICAR (an AMPK activator) for 14 weeks. Renal functional and structural studies along with electron microscopy were performed. Mice given the high-fat diet had proximal tubule injury with the presence of enlarged clear vacuoles, and multilaminar inclusions concurrent with an increase of tissue lipid and overloading of the lysosomal system. The margins of the clear vacuoles were positive for the endolysosomal marker, LAMP1, suggesting lysosome accumulation. Characterization of vesicles by special stains (Oil Red O, Nile Red, Luxol Fast Blue) and by electron microscopy showed they contained onion skin-like accumulations consistent with phospholipids. Moreover, cholesteryl esters and phosphatidylcholine-containing phospholipids were significantly increased in the kidneys of mice on a high-fat diet. AMPK activation with chronic AICAR treatment prevented the clinical and structural effects of high-fat diet. Thus, high-fat diet contributes to a dysfunction of the lysosomal system and altered lipid metabolism characterized by cholesterol and phospholipid accumulation in the kidney. AMPK activation normalizes the changes in renal lipid content despite chronic exposure to lipid challenge.

0 comments Cited 102 times – based on 0 reviews      Review now

Bookmark

Record: found
Abstract: found
Article: found

Is Open Access

Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging

Robert A. Bailey, Yiting Wang, Vivienne Zhu … (2014)

Background Kidney Disease Improving Global Outcomes (KDIGO) 2013 updated the classification and risk stratification of chronic kidney disease (CKD) to include both the level of renal function and urinary albumin excretion (UAE). The update subclassifies the previous category of moderate renal impairment. There is currently limited information on the prevalence of CKD based on this new classification in United States (US) adults with type 2 diabetes mellitus (T2DM). The objective of this study was to provide such estimates, for T2DM both overall and in those ≥ 65 years of age. We used the continuous National Health and Nutrition Examination Survey (NHANES) 1999–2012 to identify participants with T2DM. Estimated glomerular filtration rate (eGFR) and UAE were calculated using laboratory results and data collected from the surveys, and categorized based on the KDIGO classification. Projections for the US T2DM population were based on NHANES sampling weights. Results A total of 2915 adults diagnosed with T2DM were identified from NHANES, with 1466 being age ≥ 65 years. Prevalence of CKD based on either eGFR or UAE was 43.5% in the T2DM population overall, and 61.0% in those age ≥ 65 years. The prevalence of mildly decreased renal function or worse (eGFR 30 mg/g) was 32.2% overall and 39.1% in those age ≥ 65 years. The most common comorbidities were hypertension, retinopathy, coronary heart disease, myocardial infarction, and congestive heart failure. Conclusions This study confirms the high prevalence of CKD in T2DM, impacting 43.5% of this population. Additionally, this study is among the first to report US prevalence estimates of CKD based on the new KDIGO CKD staging system.

0 comments Cited 95 times – based on 0 reviews      Review now

Bookmark

All references

Author and article information

Contributors

Utpal Sen: Role: Editor

Journal

Journal ID (nlm-ta): PLoS One

Journal ID (iso-abbrev): PLoS ONE

Journal ID (publisher-id): plos

Journal ID (pmc): plosone

Title: PLoS ONE

Publisher: Public Library of Science (San Francisco, CA USA )

ISSN (Electronic): 1932-6203

Publication date (Electronic): 22 February 2017

Publication date Collection: 2017

Volume: 12

Issue: 2

Electronic Location Identifier: e0172644

Affiliations

[1 ]Department of Medicine, Kolling Institute, University of Sydney, Sydney, Australia

[2 ]Department of Diabetes, Endocrinology and Metabolism, Royal North Shore Hospital, St Leonards, NSW, Australia

[3 ]School of Life Sciences, Faculty of Science, University of Technology Sydney, Sydney, Australia

[4 ]Department of Anatomical Pathology, Royal North Shore Hospital, St Leonards, NSW, Australia

University of Louisville, UNITED STATES

Author notes

Competing Interests: The authors have declared that no competing interests exist.

Conceptualization: SJG CAP HC SS.
Formal analysis: SJG HC SS.
Funding acquisition: SJG CAP SS.
Investigation: SJG MT RT RTM AZ MGW JC HC.
Methodology: SJG CAP HC SS.
Writing – original draft: SJG.
Writing – review & editing: SJG HC RTM CAP SS.

* E-mail: sarah.glastras@ 123456sydney.edu.au

Article

Publisher ID: PONE-D-16-41431

DOI: 10.1371/journal.pone.0172644

PMC ID: 5321436

PubMed ID: 28225809

SO-VID: 75da3e42-5a07-4c74-a4d2-449a27ca5bbf

License:

This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

History

Date received : 17 October 2016

Date accepted : 7 February 2017

Page count

Figures: 8, Tables: 1, Pages: 17

Funding

Funded by: funder-id http://dx.doi.org/10.13039/100008713, Diabetes Australia Research Trust;

Award Recipient : Carol A. Pollock

This study was funded by Diabetes Australia; Diabetes Australia Research Trust grant Y15G-POLC awarded to S.J.G., C.A.P., and S.S. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.

Custom metadata

Data Availability All relevant data are within the paper and other files can be found at figshare ( https://figshare.com/projects/The_renal_consequences_of_maternal_obesity_in_offspring_are_overwhelmed_by_postnatal_high_fat_diet/18553).

The renal consequences of maternal obesity in offspring are overwhelmed by postnatal high fat diet

Read this article at

Abstract

Aims/Hypothesis

Methods

Results

Conclusion

Related collections

PLOS Climate

Most cited references 28

Association of maternal weight gain in pregnancy with offspring obesity and metabolic and vascular traits in childhood.

Regulation of lipid accumulation by AMP-activated kinase [corrected] in high fat diet-induced kidney injury.

Chronic kidney disease in US adults with type 2 diabetes: an updated national estimate of prevalence based on Kidney Disease: Improving Global Outcomes (KDIGO) staging

Author and article information

Contributors

Journal

Affiliations

Author notes

Article

History

Page count

Funding

Categories

Custom metadata

Comments

Comment on this article

Similar content 86

Cited by 16

Most referenced authors 572