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Reproductive Biology and Endocrinology
Published in: Reproductive Biology and Endocrinology 1/2018

Open Access 01-12-2018 | Research

Physiological, mitochondrial, and oxidative stress differences in the presence or absence of lactation in rats

Authors: Hayden W. Hyatt, Yufeng Zhang, Wendy R. Hood, Andreas N. Kavazis

Published in: Reproductive Biology and Endocrinology | Issue 1/2018

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Abstract

Background

Human epidemiological data show that breastfeeding reduces the mother’s probability of developing several disease conditions, including obesity and type II diabetes compared to mothers that give birth but do not breastfeed. The goal of this investigation was to characterize how lactation changes a rat’s body composition, metabolism, mitochondrial function, and oxidative stress.

Methods

Ten-week old female Sprague-Dawley rats were divided into three groups (n = 8 per group): 1) non-reproductive (NR), 2) those that were allowed to mate and give birth, but were not allowed to suckle their pups (PP), and 3) those that were allowed to mate and give birth, and suckled their young until weaning at 21 days (PL). All animals were sacrificed at a time corresponding to 7 days following the weaning of pups (i.e., day 28 postpartum).

Results

The body mass of PL rats was similar to NR rats, but the body mass of PP rats was higher than NR rats. Importantly, PL rats had lower retroperitoneal white adipose tissue mass compared to both NR and PP rats. The difference in fat mass was accompanied by higher protein levels of PPARδ, SOD2, and reduced oxidative damage. Furthermore, the liver of PL rats had higher mitochondrial function with NADH-linked substrates, and higher expression of PGC-1α, PPARδ, and SOD2.

Conclusions

These acute differences observed between female rats that did and did not suckle their young could be used as the foundation for future research investigating the prolonged and sustained benefits of lactation.
Literature
1.
Colberg SR, Sigal RJ, Fernhall B, Regensteiner JG, Blissmer BJ, Rubin RR, Chasan-Taber L, Albright AL, Braun B. American College of Sports M, American diabetes a: exercise and type 2 diabetes: the American College of Sports Medicine and the American Diabetes Association: joint position statement. Diabetes Care. 2010;33:e147–67.CrossRefPubMedPubMedCentral
2.
Klempel MC, Kroeger CM, Bhutani S, Trepanowski JF, Varady KA. Intermittent fasting combined with calorie restriction is effective for weight loss and cardio-protection in obese women. Nutr J. 2012;11:98.CrossRefPubMedPubMedCentral
3.
Thomas JA 2nd, Antonelli JA, Lloyd JC, Masko EM, Poulton SH, Phillips TE, Pollak M, Freedland SJ. Effect of intermittent fasting on prostate cancer tumor growth in a mouse model. Prostate Cancer Prostatic Dis. 2010;13:350–5.CrossRefPubMed
4.
Heilbronn LK, Ravussin E. Calorie restriction and aging: review of the literature and implications for studies in humans. Am J Clin Nutr. 2003;78:361–9.PubMed
5.
Natland ST, Lund Nilsen T, Midthjell K, Frost A, Forsmo S. Lactation and cardiovascular risk factors in mothers in a population-based study: the HUNT-study. Int Breastfeed J. 2012;7:8.CrossRefPubMedPubMedCentral
6.
Ram KT, Bobby P, Hailpern SM, Lo JC, Schocken M, Skurnick J, Santoro N. Duration of lactation is associated with lower prevalence of the metabolic syndrome in midlife—SWAN, the study of women’s health across the nation. Am J Obstet Gynecol. 2008;198:268. e261-e266CrossRefPubMedPubMedCentral
7.
Stuebe AM, Kleinman K, Gillman MW, Rifas-Shiman SL, Gunderson EP, Rich-Edwards J. Duration of lactation and maternal metabolism at 3 years postpartum. J Women's Health. 2010;19:941–50.CrossRef
8.
Stuebe AM, Michels KB, Willett WC, Manson JE, Rexrode K, Rich-Edwards JW. Duration of lactation and incidence of myocardial infarction in middle to late adulthood. Am J Obstet Gynecol. 2009;200:138. e131-138. e138CrossRefPubMed
9.
Stuebe AM, Rich-Edwards JW. The reset hypothesis: lactation and maternal metabolism. Am J Perinatol. 2009;26:81.CrossRefPubMed
10.
Ramos P, Herrera E. Effect of prolonged glucose infusion on insulin sensitivity in the conscious normal rat. Horm Metab Res. 1995;27:197–200.CrossRefPubMed
11.
Martin A, Zorzano A, Caruncho I, Herrera E. Glucose tolerance tests and “in vivo” response to intravenous insulin in the unanaesthesized late pregnant rat and their consequences to the fetus. Diabete Metab. 1986;12:302–7.PubMed
12.
Einstein FH, Fishman S, Muzumdar RH, Yang XM, Atzmon G, Barzilai N. Accretion of visceral fat and hepatic insulin resistance in pregnant rats. Am J Physiol Endocrinol Metab. 2008;294:E451–5.CrossRefPubMed
13.
Jones RG, Ilic V, Williamson DH. Physiological significance of altered insulin metabolism in the conscious rat during lactation. Biochem J. 1984;220:455–60.CrossRefPubMedPubMedCentral
14.
Hamosh M, Clary TR, Chernick SS, Scow RO. Lipoprotein lipase activity of adipose and mammary tissue and plasma triglyceride in pregnant and lactating rats. Biochim Biophys Acta. 1970;210:473–82.CrossRefPubMed
15.
Rolfe DF, Brown GC. Cellular energy utilization and molecular origin of standard metabolic rate in mammals. Physiol Rev. 1997;77:731–58.CrossRefPubMed
16.
Gutgesell A, Ringseis R, Schmidt E, Brandsch C, Stangl GI, Eder K. Downregulation of peroxisome proliferator-activated receptor α and its coactivators in liver and skeletal muscle mediates the metabolic adaptations during lactation in mice. J Mol Endocrinol. 2009;43:241–50.CrossRefPubMed
17.
Pichaud N, Garratt M, Ballard JW, Brooks RC. Physiological adaptations to reproduction. II. Mitochondrial adjustments in livers of lactating mice. J Exp Biol. 2013;216:2889–95.CrossRefPubMed
18.
Speakman JR, Garratt M. Oxidative stress as a cost of reproduction: beyond the simplistic trade-off model. BioEssays. 2014;36:93–106.CrossRefPubMed
19.
Hyatt HW, Kephart WC, Holland AM, Mumford P, Mobley CB, Lowery RP, Roberts MD, Wilson JM, Kavazis AN. A Ketogenic diet in rodents elicits improved mitochondrial adaptations in response to resistance exercise training compared to an Isocaloric western diet. Front Physiol. 2016;7:533.PubMedPubMedCentral
20.
Mowry AV, Kavazis AN, Sirman AE, Potts WK, Hood WR. Reproduction does not adversely affect liver mitochondrial respiratory function but results in lipid peroxidation and increased antioxidants in house mice. PLoS One. 2016;11:e0160883.CrossRefPubMedPubMedCentral
21.
Messer JI, Jackman MR, Willis WT. Pyruvate and citric acid cycle carbon requirements in isolated skeletal muscle mitochondria. Am J Physiol Cell Physiol. 2004;286:C565–72.CrossRefPubMed
22.
Wanders RJ, Groen AK, Van Roermund CW, Tager JM. Factors determining the relative contribution of the adenine-nucleotide translocator and the ADP-regenerating system to the control of oxidative phosphorylation in isolated rat-liver mitochondria. Eur J Biochem. 1984;142:417–24.CrossRefPubMed
23.
Estabrook RW. [7] mitochondrial respiratory control and the polarographic measurement of ADP: O ratios. Methods Enzymol. 1967;10:41–7.CrossRef
24.
Kavazis AN, Talbert EE, Smuder AJ, Hudson MB, Nelson WB, Powers SK. Mechanical ventilation induces diaphragmatic mitochondrial dysfunction and increased oxidant production. Free Radic Biol Med. 2009;46:842–50.CrossRefPubMedPubMedCentral
25.
Trounce IA, Kim YL, Jun AS, Wallace DC. Assessment of mitochondrial oxidative phosphorylation in patient muscle biopsies, lymphoblasts, and transmitochondrial cell lines. Methods Enzymol. 1996;264:484–509.CrossRefPubMed
26.
Bradford MM. A rapid and sensitive method for the quantitation of microgram quantities of protein utilizing the principle of protein-dye binding. Anal Biochem. 1976;72:248–54.CrossRefPubMed
27.
Barja G. Mitochondrial oxygen radical generation and leak: sites of production in states 4 and 3, organ specificity, and relation to aging and longevity. J Bioenerg Biomembr. 1999;31:347–66.CrossRefPubMed
28.
Wu Z, Puigserver P, Andersson U, Zhang C, Adelmant G, Mootha V, Troy A, Cinti S, Lowell B, Scarpulla RC, Spiegelman BM. Mechanisms controlling mitochondrial biogenesis and respiration through the thermogenic coactivator PGC-1. Cell. 1999;98:115–24.CrossRefPubMed
29.
Lee CH, Olson P, Hevener A, Mehl I, Chong LW, Olefsky JM, Gonzalez FJ, Ham J, Kang H, Peters JM, Evans RM. PPARdelta regulates glucose metabolism and insulin sensitivity. Proc Natl Acad Sci U S A. 2006;103:3444–9.CrossRefPubMedPubMedCentral
30.
Roberts LD, Murray AJ, Menassa D, Ashmore T, Nicholls AW, Griffin JL. The contrasting roles of PPARδ and PPARg in regulating the metabolic switch between oxidation and storage of fats in white adipose tissue. Genome Biol. 2011;12:R75.CrossRefPubMedPubMedCentral
31.
Barnosky AR, Hoddy KK, Unterman TG, Varady KA. Intermittent fasting vs daily calorie restriction for type 2 diabetes prevention: a review of human findings. Transl Res. 2014;164:302–11.CrossRefPubMed
32.
Ross R, Dagnone D, Jones PJ, Smith H, Paddags A, Hudson R, Janssen I. Reduction in obesity and related comorbid conditions after diet-induced weight loss or exercise-induced weight loss in men. A randomized, controlled trial. Ann Intern Med. 2000;133:92–103.CrossRefPubMed
33.
Speakman J, McQueenie J. Limits to sustained metabolic rate: the link between food intake, basal metabolic rate, and morphology in reproducing mice, Mus Musculus. Physiol Zool. 1996;69:746–69.CrossRef
34.
Moore BJ, Brasel JA. One cycle of reproduction consisting of pregnancy, lactation or no lactation, and recovery: effects on fat pad cellularity in ad libitum-fed and food-restricted rats. J Nutr. 1984;114:1560–5.CrossRefPubMed
35.
Moore BJ, Brasel JA. One cycle of reproduction consisting of pregnancy, lactation or no lactation, and recovery: effects on carcass composition in ad libitum-fed and food-restricted rats. J Nutr. 1984;114:1548–59.CrossRefPubMed
36.
Moore BJ, Olsen JL, Marks F, Brasel JA. The effects of high fat feeding during one cycle of reproduction consisting of pregnancy, lactation and recovery on body composition and fat pad cellularity in the rat. J Nutr. 1984;114:1566–73.CrossRefPubMed
37.
Stuebe AM, Rich-Edwards JW, Willett WC, Manson JE, Michels KB. Duration of lactation and incidence of type 2 diabetes. JAMA. 2005;294:2601–10.CrossRefPubMed
38.
Sanderson LM, Boekschoten MV, Desvergne B, Muller M, Kersten S. Transcriptional profiling reveals divergent roles of PPARalpha and PPARbeta/delta in regulation of gene expression in mouse liver. Physiol Genomics. 2010;41:42–52.CrossRefPubMed
39.
Powers SK, Ji L, Leeuwenburgh C. Exercise training-induced alterations in skeletal muscle antioxidant capacity: a brief review. Med Sci Sports Exerc. 1999;31:987–97.CrossRefPubMed
40.
Baynes JW. Role of oxidative stress in development of complications in diabetes. Diabetes. 1991;40:405–12.CrossRefPubMed
41.
Furukawa S, Fujita T, Shimabukuro M, Iwaki M, Yamada Y, Nakajima Y, Nakayama O, Makishima M, Matsuda M, Shimomura I. Increased oxidative stress in obesity and its impact on metabolic syndrome. J Clin Invest. 2004;114:1752–61.CrossRefPubMedPubMedCentral
42.
43.
Monaghan P, Metcalfe NB, Torres R. Oxidative stress as a mediator of life history trade-offs: mechanisms, measurements and interpretation. Ecol Lett. 2009;12:75–92.CrossRefPubMed
44.
Lu Z, Xu X, Hu X, Fassett J, Zhu G, Tao Y, Li J, Huang Y, Zhang P, Zhao B, Chen Y. PGC-1 alpha regulates expression of myocardial mitochondrial antioxidants and myocardial oxidative stress after chronic systolic overload. Antioxid Redox Signal. 2010;13:1011–22.CrossRefPubMedPubMedCentral
Metadata
Title
Physiological, mitochondrial, and oxidative stress differences in the presence or absence of lactation in rats
Authors
Hayden W. Hyatt
Yufeng Zhang
Wendy R. Hood
Andreas N. Kavazis
Publication date
01-12-2018
Publisher
BioMed Central
Published in
Reproductive Biology and Endocrinology / Issue 1/2018
Electronic ISSN: 1477-7827
DOI
https://doi.org/10.1186/s12958-017-0317-7

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