Impact of High-Fat Diet and Obesity on Energy Balance and Fuel Utilization During the Metabolic Challenge of Lactation

Department of Obstetrics and Gynecology, Division of Basic Reproductive Sciences, University of Colorado, Denver, Colorado, USA.
Obesity (Impact Factor: 3.73). 06/2011; 20(1):65-75. DOI: 10.1038/oby.2011.196
Source: PubMed

ABSTRACT The effects of obesity and a high-fat (HF) diet on whole body and tissue-specific metabolism of lactating dams and their offspring were examined in C57/B6 mice. Female mice were fed low-fat (LF) or HF diets before and throughout pregnancy and lactation. HF-fed mice were segregated into lean (HF-Ln) and obese (HF-Ob) groups before pregnancy by their weight gain response. Compared to LF-Ln dams, HF-Ln, and HF-Ob dams exhibited a greater positive energy balance (EB) and increased dietary fat retention in peripheral tissues (P < 0.05). HF-Ob dams had greater dietary fat retention in liver and adipose compared to HF-Ln dams (P < 0.05). De novo synthesized fat was decreased in tissues and milk from HF-fed dams compared to LF-Ln dams (P < 0.05). However, less dietary and de novo synthesized fat was found in the HF-Ob mammary glands compared to HF-Ln (P < 0.05). Obesity was associated with reduced milk triglycerides relative to lean controls (P < 0.05). Compared to HF diet alone obesity has additional adverse affects, impairing both lipid metabolism as well as milk fat production. Growth rates of LF-Ln litters were lower than HF-Ln and HF-Ob litters (P < 0.05). Total energy expenditure (TEE) of HF-Ob litters was reduced relative to HF-Ln litters, whereas their respiratory exchange ratios (RERs) were increased (P < 0.05). Collectively these data show that consumption of a HF diet significantly affects maternal and neonatal metabolism and that maternal obesity can independently alter these responses.

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    • "Twenty female C57BL/6J (C57B6) mice were purchased from Jackson Labs (Bar Harbor, Maine) at 7 weeks of age. After 1 week of acclimation, 5 mice were placed on a defined low fat (LF) diet (68% kcal carbohydrate, 12% kcal fat; #D08032201, Research Diets, New Brunswick NJ) and 15 mice were placed on a defined high fat (HF) diet (34% kcal carbohydrate, 46% kcal fat; #D08032202, Research Diets) for the duration of the study [19]. The LF and HF diets differed only in their relative amounts of carbohydrate (starch) and fat (soy oil) calories. "
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    ABSTRACT: Maternal metabolic and nutrient trafficking adaptations to lactation differ among lean and obese mice fed a high fat (HF) diet. Obesity is thought to impair milk lipid production, in part, by decreasing trafficking of dietary and de novo synthesized lipids to the mammary gland. Here, we report that de novo lipogenesis regulatory mechanisms are disrupted in mammary glands of lactating HF-fed obese (HF-Ob) mice. HF feeding decreased the total levels of acetyl-CoA carboxylase-1 (ACC), and this effect was exacerbated in obese mice. The relative levels of phosphorylated (inactive) ACC, were elevated in the epithelium, and decreased in the adipose stroma, of mammary tissue from HF-Ob mice compared to those of HF-fed lean (HF-Ln) mice. Mammary gland levels of AMP-activated protein kinase (AMPK), which catalyzes formation of inactive ACC, were also selectively elevated in mammary glands of HF-Ob relative to HF-Ln dams or to low fat fed dams. These responses correlated with evidence of increased lipid retention in mammary adipose, and decreased lipid levels in mammary epithelial cells, of HF-Ob dams. Collectively, our data suggests that maternal obesity impairs milk lipid production, in part, by disrupting the balance of de novo lipid synthesis in the epithelial and adipose stromal compartments of mammary tissue through processes that appear to be related to increased mammary gland AMPK activity, ACC inhibition, and decreased fatty acid synthesis.
    PLoS ONE 05/2014; 9(5):e98066. DOI:10.1371/journal.pone.0098066 · 3.23 Impact Factor
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    • "Three separate cohorts of mice were placed in a metabolic monitoring system that provided measurements of energy balance (intake and expenditure), the respiratory exchange ratio (RER), and activity levels (Columbus 8M Oxymax) [37]. Mice were individually housed in metabolic chambers and allowed to acclimate for one week prior to fasting and refeeding. "
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    ABSTRACT: Cytoplasmic lipid droplets (CLD) are organelle-like structures that function in neutral lipid storage, transport and metabolism through the actions of specific surface-associated proteins. Although diet and metabolism influence hepatic CLD levels, how they affect CLD protein composition is largely unknown. We used non-biased, shotgun, proteomics in combination with metabolic analysis, quantitative immunoblotting, electron microscopy and confocal imaging to define the effects of low-and high-fat diets on CLD properties in fasted-refed mice. We found that the hepatic CLD proteome is distinct from that of CLD from other mammalian tissues, containing enzymes from multiple metabolic pathways. The hepatic CLD proteome is also differentially affected by dietary fat content and hepatic metabolic status. High fat feeding markedly increased the CLD surface density of perilipin-2, a critical regulator of hepatic neutral lipid storage, whereas it reduced CLD levels of betaine-homocysteine S-methyltransferase, an enzyme regulator of homocysteine levels linked to fatty liver disease and hepatocellular carcinoma. Collectively our data demonstrate that the hepatic CLD proteome is enriched in metabolic enzymes, and that it is qualitatively and quantitatively regulated by diet and metabolism. These findings implicate CLD in the regulation of hepatic metabolic processes, and suggest that their properties undergo reorganization in response to hepatic metabolic demands.
    PLoS ONE 07/2013; 8(7). DOI:10.1371/journal.pone.0067631 · 3.23 Impact Factor
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