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Alterations of Mitochondrial Function and Metabolism in Skeletal Muscle, Liver, and White Adipose: Early Evidence for the Lactation Reset Hypothesis
Author(s) -
Hyatt Hayden W,
Zhang Yufeng,
Hood Wendy R,
Kavazis Andreas N
Publication year - 2017
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.31.1_supplement.1086.7
Subject(s) - endocrinology , medicine , lactation , skeletal muscle , white adipose tissue , brown adipose tissue , biology , weaning , mitochondrion , adipose tissue , respiration , pregnancy , anatomy , biochemistry , genetics
Lactation following reproduction serves as one of the largest metabolic challenges a female experiences in their lifetime. As such, the lactation reset hypothesis has been proposed to explain changes in metabolism that confers protective health benefits (e.g., fewer visceral adipocytes, lower fasting glucose, increased insulin sensitivity, etc.) in mothers that breast‐feed their children. PURPOSE The aim of the current experiment was to discern mitochondrial function differences and changes in markers of metabolism in female rats that nurse their pups to weaning compared to rats that reproduce but do not nurse their pups or do not reproduce. METHODS Female Sprague‐Dawley rats were assigned to one of three groups: 1) gave birth and nursed their pups for 21 days and were sacrificed seven days later (PL), 2) age‐matched that gave birth but had pups removed and thus did not nurse (P), and 3) age‐matched that did not reproduce (NR). Liver and skeletal muscle were dissected immediately following sacrifice and mitochondria were isolated using differential centrifugation for measurements of respiration utilizing high resolution respirometry. Liver, skeletal muscle, and white adipose tissue were stored for western blot analysis. RESULTS Liver mass was higher in PL compared to NR (p<0.01) and P (p=0.03). PL and P exhibited higher state 3 respiration in liver mitochondria when utilizing complex I substrates (i.e., pyruvate and malate) compared to NR (p=0.03 and p=0.05, respectively). Noteworthy, PL demonstrated lower respiratory control ratio in liver mitochondria when utilizing complex II substrates compared to NR (p=0.03) and P (p=0.02). No differences in skeletal muscle mitochondria respiration were detected (p>0.05). Protein levels of superoxide dismutase 2 (SOD2) in the liver were higher in PL compared to NR (p=0.01) and P (p=0.05). Peroxisome proliferator‐activated receptor gamma coactivator 1‐alpha (PGC‐1a) protein was higher in liver of PL compared to NR (p<0.01) and higher in P compared to NR (p=0.05). Catalase (CAT) protein levels in liver were higher in P (p=0.04) and PL (p=0.05) compared to NR. There were no differences in superoxide dismutase 1 (SOD1), glutathione peroxidase (GPX), and peroxisome proliferator activated receptor delta (PPAR‐δ) protein expression (p>0.05) in liver. WAT protein expression of PPAR‐d was higher in PL animals compared to NR (p<0.01) and P (p=0.05). No differences (p>0.05) were observed in WAT protein expression for GPX, CAT, SOD1, SOD2, PGC‐1a. CONCLUSION The taxing metabolic event of lactation produces systemic alterations in metabolism and liver mitochondrial function that persist a week after the cessation of nursing in rats, which may, in part, explain the beneficial effects of breast‐feeding. Support or Funding Information Funded by NIH R03HD083654