title: Compared to casein, bovine lactoferrin reduces plasma leptin and corticosterone and affects hypothalamic gene expression without altering weight gain or fat mass in high fat diet fed C57/BL6J mice.
abstract: BACKGROUND
  Several studies in both humans and rodents have examined the use of lactoferrin as a dietary solution to weight gain and visceral fat accretion and have shown promising results in the short term (up to 7 weeks). This study examined the effects of giving lactoferrin over a longer period of time.
  
  
  METHODS
  For 13 weeks, male C57/BL6J mice were given a diet containing 10 % kJ fat and 20 % kJ casein (LFD) or a diet with 45 % kJ fat and either 20 % kJ casein (HFD) or 20 % kJ lactoferrin (HFD + Lac). Physiological, metabolic, and biochemical parameters were investigated. Gene expression was investigated by Real-Time PCR and microarray. All data was assessed using t-test, ANOVA or ANCOVA. Gene Set Enrichment Analysis was used to interpret microarray data and assess the impact on gene sets with common biological roles.
  
  
  RESULTS
  By the end of the trial, HFD + Lac fed mice did not alter energy balance, body composition, bodyweight, or weight gain when compared to the HFD group. Notably, there were no changes in subcutaneous or epididymal adipose leptin mRNA levels between high fat diet groups, however plasma leptin was significantly reduced in the HFD + Lac compared to HFD group (P < 0.05) suggesting reduced leptin secretion. Global microarray analysis of the hypothalamus indicate an overall reduction in gene sets associated with feeding behaviour (P < 0.01) and an up-regulation of gene sets associated with retinol metabolism in the HFD + Lac group compared to the HFD group (P < 0.01). Genes in the latter catergory have been shown to impact on the hypothalamic-pituitary-adrenal axis. Notably, plasma corticosterone levels in the HFD + Lac group were reduced compared to the HFD fed mice (P < 0.05).
  
  
  CONCLUSIONS
  The data suggests that prolonged feeding of full-length dietary lactoferrin, as part of a high fat diet, does not have a beneficial impact on weight gain when compared to casein. However, its impact on leptin secretion and accompanying changes in hypothalamic gene expression may underlie how this dietary protein alters plasma corticosterone. The lactoferrin fed mouse model could be used to identify leptin and corticosterone regulated genes in the hypothalamus without the confounding effects of body weight change.
authors.affiliation: Teagasc, Moorepark Food Research Centre, Fermoy, County Cork, Ireland ; Faculty of Medicine, Pharmacology, Medical Nutrition Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Bettina
authors.initials: B
authors.lastname: McManus
authors.affiliation: Faculty of Medicine, Pharmacology, Medical Nutrition Physiology, University of Helsinki, Helsinki, Finland.
authors.forename: Riitta
authors.initials: R
authors.lastname: Korpela
authors.affiliation: Teagasc, Moorepark Food Research Centre, Fermoy, County Cork, Ireland.
authors.forename: Paula
authors.initials: P
authors.lastname: O'Connor
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors.forename: Harriet
authors.initials: H
authors.lastname: Schellekens
authors.affiliation: Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland ; Department of Anatomy & Neuroscience, University College Cork, Cork, Ireland.
authors.forename: John F
authors.initials: JF
authors.lastname: Cryan
authors.affiliation: Teagasc, Moorepark Food Research Centre, Fermoy, County Cork, Ireland ; Alimentary Pharmabiotic Centre, University College Cork, Cork, Ireland.
authors.forename: Paul D
authors.initials: PD
authors.lastname: Cotter
authors.affiliation: Teagasc, Moorepark Food Research Centre, Fermoy, County Cork, Ireland.
authors.forename: Kanishka N
authors.initials: KN
authors.lastname: Nilaweera
keywords: Corticosterone; Fat mass; High fat diet; Hypothalamus; Lactoferrin; Leptin; Microarray; Obesity; Weight gain