title: Effects of Anthocyanin and Flavanol Compounds on Lipid Metabolism and Adipose Tissue Associated Systemic Inflammation in Diet-Induced Obesity.
abstract: Background. Naturally occurring substances from the flavanol and anthocyanin family of polyphenols have been proposed to exert beneficial effects in the course of obesity. We hypothesized that their effects on attenuating obesity-induced dyslipidemia as well as the associated inflammatory sequelae especially have health-promoting potential. Methods. Male C57BL/6J mice (n = 52) received a control low-fat diet (LFD; 10 kcal% fat) for 6 weeks followed by 24 weeks of either LFD (n = 13) or high-fat diet (HFD; 45 kcal% fat; n = 13) or HFD supplemented with 0.1% w/w of the flavanol compound epicatechin (HFD+E; n = 13) or an anthocyanin-rich bilberry extract (HFD+B; n = 13). Energy substrate utilization was determined by indirect calorimetry in a subset of mice following the dietary switch and at the end of the experiment. Blood samples were collected at baseline and at 3 days and 4, 12, and 20 weeks after dietary switch and analyzed for systemic lipids and proinflammatory cytokines. Adipose tissue (AT) histopathology and inflammatory gene expression as well as hepatic lipid content were analyzed after sacrifice. Results. The switch from a LFD to a HFD lowered the respiratory exchange ratio and increased plasma cholesterol and hepatic lipid content. These changes were not attenuated by HFD+E or HFD+B. Furthermore, the polyphenol compounds could not prevent HFD-induced systemic rise of TNF-α levels. Interestingly, a significant reduction in Tnf gene expression in HFD+B mice was observed in the AT. Furthermore, HFD+B, but not HFD+E, significantly prevented the early upregulation of circulating neutrophil chemoattractant mKC. However, no differences in AT histopathology were observed between the HFD types. Conclusion. Supplementation of HFD with an anthocyanin-rich bilberry extract but not with the flavanol epicatechin may exert beneficial effects on the systemic early inflammatory response associated with diet-induced obesity. These systemic effects were transient and not observed after prolongation of HFD-feeding (24 weeks). On the tissue level, long-term treatment with bilberry attenuated TNF-α expression in adipose tissue.
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands; Top Institute Food and Nutrition, 6709 AN Wageningen, Netherlands.
authors.forename: Roel A
authors.identifier: 0000-0002-9516-5195
authors.initials: RA
authors.lastname: van der Heijden
authors.affiliation: Top Institute Food and Nutrition, 6709 AN Wageningen, Netherlands; Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, Netherlands.
authors.forename: Martine C
authors.initials: MC
authors.lastname: Morrison
authors.affiliation: Department of Epidemiology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Fareeba
authors.initials: F
authors.lastname: Sheedfar
authors.affiliation: Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, Netherlands.
authors.forename: Petra
authors.initials: P
authors.lastname: Mulder
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Marijke
authors.initials: M
authors.lastname: Schreurs
authors.affiliation: Avans University of Applied Sciences, 5223 DE Breda, Netherlands.
authors.forename: Pascal P H
authors.initials: PP
authors.lastname: Hommelberg
authors.affiliation: Molecular Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Marten H
authors.initials: MH
authors.lastname: Hofker
authors.affiliation: Department of Internal Medicine, Maastricht University Medical Centre, Maastricht University, 6229 HX Maastricht, Netherlands.
authors.forename: Casper
authors.initials: C
authors.lastname: Schalkwijk
authors.affiliation: Top Institute Food and Nutrition, 6709 AN Wageningen, Netherlands; Department of Metabolic Health Research, Netherlands Organisation for Applied Scientific Research (TNO), 2333 CK Leiden, Netherlands.
authors.forename: Robert
authors.initials: R
authors.lastname: Kleemann
authors.affiliation: Department of Pediatrics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Uwe J F
authors.initials: UJ
authors.lastname: Tietge
authors.affiliation: Molecular Genetics, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands.
authors.forename: Debby P Y
authors.initials: DP
authors.lastname: Koonen
authors.affiliation: Department of Pathology and Medical Biology, University Medical Center Groningen, University of Groningen, 9713 GZ Groningen, Netherlands; Top Institute Food and Nutrition, 6709 AN Wageningen, Netherlands.
authors.forename: Peter
authors.initials: P
authors.lastname: Heeringa
mesh_terms: D000273:Adipose Tissue / Q000187:drug effects*; D000818:Animals; D000872:Anthocyanins / Q000627:therapeutic use*; D018752:Diet, Fat-Restricted; D059305:Diet, High-Fat / Q000009:adverse effects; D044950:Flavanones / Q000627:therapeutic use*; D007249:Inflammation / Q000188:drug therapy* / Q000276:immunology / Q000378:metabolism; D050356:Lipid Metabolism / Q000187:drug effects*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009765:Obesity / Q000276:immunology* / Q000378:metabolism; D010936:Plant Extracts / Q000627:therapeutic use; D014409:Tumor Necrosis Factor-alpha / Q000378:metabolism; D029800:Vaccinium myrtillus / Q000737:chemistry
chemical_list: D000872:Anthocyanins; D044950:Flavanones; D010936:Plant Extracts; D014409:Tumor Necrosis Factor-alpha; C028610:flavanone