Differences in adipocyte long chain fatty acid uptake in Osborne–Mendel and S5B/Pl rats in response to high-fat diets

Petrescu, Oana; Cheema, Amina; Fan, Xinqing; Berk, Paul D.

doi:10.1038/sj.ijo.0803792

Cited by 15 publications

(14 citation statements)

References 52 publications

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“…Thus these data are not consistent with the hypothesis that maternal obesity programs an increase in adipocyte number. Consistent with previous reports (2,36,40), we did detect an effect of offspring HF diet consumption on adipocyte size. There was no effect on cell number, but results differ in the literature about the effect of a HF diet on hyperplasia (2,19,28,33,40).…”

Section: Discussionsupporting

confidence: 92%

Maternal obesity is necessary for programming effect of high-fat diet on offspring

White

Purpera²,

Morrison³

2009

American Journal of Physiology-Regulatory, Integrative and Comp

170

149

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We tested the hypothesis that maternal consumption of dietary fat, independent from obesity, increases serum leptin in neonatal pups and predisposes them to adult obesity. Female rats either were fed a high-fat (HF) diet or a low-fat (LF) diet or were fed the HF diet but pair fed (PF) to the caloric intake of the LF group for 4 wk before breeding and throughout gestation and lactation. Dams consuming the HF diet had increased adiposity and were hyperphagic. At weaning, pups born to obese dams had significantly higher body fat and serum leptin levels and reduced insulin tolerance compared with offspring of LF-fed dams. Pups were weaned onto a chow diet until 8 wk of age, when they were then fed either HF or LF diet. At 18 wk of age, offspring from obese HF dams weighed more than offspring from nonobese LF or PF dams, and offspring eating HF diet weighed significantly more than those eating LF diet. Consequently, HF-fed offspring of obese HF dams weighed the most and LF-fed offspring from obese HF dams were similar in weight to HF-fed offspring from nonobese LF dams. These data suggest that maternal obesity exerts an independent effect on offspring body weight that is of similar magnitude as the effect of the offspring's adult diet. Furthermore, there was no difference in body weight between the nonobese LF and PF offspring on either diet. Together, these data suggest that maternal adiposity, and not dietary fat per se, induces hyperleptinemia and insulin resistance in offspring, as well as an increased body weight that persists into adulthood.

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Section: Discussionsupporting

confidence: 92%

Maternal obesity is necessary for programming effect of high-fat diet on offspring

White

Purpera²,

Morrison³

2009

American Journal of Physiology-Regulatory, Integrative and Comp

170

149

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“…For comparative studies of protein-mediated LCFA uptake, a change in V max has proven to be the most reliable single indicator of a change in uptake 35-41 . The V max for saturable uptake of [ 3 H]-oleate in control 3T3 cells was 0.26±0.04 pmol/sec/ 50,000 cells (Figure 6) 35 .…”

Section: Resultsmentioning

confidence: 99%

“…Numerous cell types display mAsp-AT on their cell surfaces 8, 10, 11, 14, 40, 43 , and key aspects of its post-mitochondrial trafficking to the plasma membrane and export from the cell via the golgi/endoplasmic reticulum have been elucidated (Berk PD, manuscript in preparation). Its regulated expression strongly correlates with rates of cellular LCFA uptake, especially in adipocytes and hepatocytes 5, 9, 37-41, 44 , and transcription rates of the gene and mAsp-AT expression on the plasma membrane parallel LCFA uptake in many experimental settings 14, 15, 35, 36, 40 . mAsp-AT antibodies not only identify the protein on the plasma membrane, but also selectively inhibit LCFA uptake 5, 9, 10, 14, 15, 35 .…”

Section: Discussionmentioning

confidence: 99%

Molecular Modeling and Functional Confirmation of a Predicted Fatty Acid Binding Site of Mitochondrial Aspartate Aminotransferase

Stump

Guarnieri

Berk

2011

Journal of Molecular Biology

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Molecular interactions are necessary for proteins to perform their functions. The identification of a putative plasma membrane fatty acid transporter as mitochondrial aspartate aminotransferase indicated that that protein must have a fatty acid binding site. Molecular modeling suggests that such a site exists in the form of a 500 Å3 hydrophobic cleft on the surface of the molecule, and identifies specific amino acid residues likely to be important for binding. The modeling and comparison with the cytosolic isoform indicated that two residues (Arg 201, Ala 219) were likely to be important to the structure and function of the binding site. These residues were mutated to determine if they were essential to that function. Expression constructs with wild-type or mutated cDNAs were produced for bacteria and eukaryotic cells. Proteins expressed in E. coli were tested for oleate binding affinity, which was decreased in the mutant proteins. 3T3 fibroblasts were transfected with expression constructs for both normal and mutated forms. Plasma membrane expression was documented by indirect immunofluorescence before [3H]-oleic acid uptake kinetics were assayed. The Vmax for uptake was significantly increased by over-expression of the wild type protein, but changed little after transfection with mutated proteins, despite their presence on the plasma membrane. The hydrophobic cleft in mitochondrial aspartate aminotransferase can serve as a fatty acid binding site. Specific residues are essential for normal fatty acid binding, without which fatty acid uptake is compromised. These results confirm the function of this protein as a fatty acid binding protein.

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“…In view of a recent study demonstrating that the body's initial responses to nutritional perturbations such as the introduction of an HFD may be quite transitory (39), we also sought to work in models in which steady-state responses to such perturbations had been achieved. We sought to conduct the studies in primarily natural, widely available, minimally invasive models in which, for example, gene knockouts did not interfere with the normal regulatory and counterregulatory responses of intermediary metabolism.…”

Section: Discussionmentioning

confidence: 99%

Insulin- and leptin-regulated fatty acid uptake plays a key causal role in hepatic steatosis in mice with intact leptin signaling but not inob/obordb/dbmice

Zhou

et al. 2010

American Journal of Physiology-Gastrointestinal and Liver Physi

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Hepatic steatosis results from several processes. To assess their relative roles, hepatocellular long-chain fatty acid (LCFA) uptake was assayed in hepatocytes from C57BL/6J control mice, mice with steatosis from a high-fat diet (HFD) or 10%, 14%, or 18% ethanol (EtOH) in drinking water [functioning leptin-signaling groups (FLSGs)], and ob/ob and db/db mice. V(max) for uptake was increased vs. controls (P < 0.001) and correlated significantly with liver weight and triglycerides (TGs) in all FLSG mice but was minimally or not increased in ob/ob and db/db mice, in which liver weights and TGs greatly exceeded projections from regressions in FLSG animals. Coefficients of determination (R(2)) for these FLSG regressions suggest that increased LCFA uptake accounts for ∼80% of the increase in hepatic TGs within these groups, but increased lipogenic gene expression data suggest that enhanced LCFA synthesis is the major contributor in ob/ob and db/db. Got2, Cd36, Slc27a2, and Slc27a5 gene expression ratios were significantly upregulated in the EtOH groups, correlating with sterol regulatory element binding protein 1c (SREBP1c) and V(max), but only Cd36 expression was increased in HFD, ob/ob, and db/db mice. Comparison of V(max) with serum insulin and leptin suggests that both hormones contribute to upregulation of uptake in the FLSG animals. Thus, increased LCFA uptake, reflecting SREBP1c-mediated upregulation of four distinct transporters, is the dominant cause of steatosis in EtOH-fed mice. In ob/ob and db/db mice, increased LCFA synthesis appears more important. In FLSG animals, insulin upregulates hepatocellular LCFA uptake. Leptin appears to upregulate LCFA uptake or to be essential for full expression of upregulation by insulin.

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Differences in adipocyte long chain fatty acid uptake in Osborne–Mendel and S5B/Pl rats in response to high-fat diets

Cited by 15 publications

References 52 publications

Maternal obesity is necessary for programming effect of high-fat diet on offspring

Maternal obesity is necessary for programming effect of high-fat diet on offspring

Molecular Modeling and Functional Confirmation of a Predicted Fatty Acid Binding Site of Mitochondrial Aspartate Aminotransferase

Insulin- and leptin-regulated fatty acid uptake plays a key causal role in hepatic steatosis in mice with intact leptin signaling but not inob/obordb/dbmice

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