title: Fat and Sucrose Intake Induces Obesity-Related Bone Metabolism Disturbances: Kinetic and Reversibility Studies in Growing and Adult Rats.
abstract: Metabolic and bone effects were investigated in growing (G, n = 45) and mature (M, n = 45) rats fed a high-fat/high-sucrose diet (HFS) isocaloric to the chow diet of controls (C, n = 30 per group). At week 19, a subset of 15 rats in each group (HFS or C, at both ages) was analyzed. Then one-half of the remaining 30 HFS rats in each groups continued HFS and one-half were shifted to C until week 27. Although no serum or bone marrow inflammation was seen, HFS increased visceral fat, serum leptin and insulin at week 19 and induced further alterations in lipid profile, serum adiponectin, and TGFβ1, TIMP1, MMP2, and MMP9, suggesting a prediabetic phenotype and cardiovascular dysfunction at week 27 more pronounced in M than G. These events were associated with dramatic reduction of osteoclastic and osteoid surfaces with accelerated mineralizing surfaces in both HFS age groups. Mineral metabolism and its major regulators were disturbed, leading to hyperphosphatemia and hypocalcemia. These changes were associated with bone alterations in the weight-bearing tibia, not in the non-weight-bearing vertebra. Indeed in fat rats, tibia trabecular bone accrual increased in G whereas loss of trabecular bone in M was alleviated. At diaphysis cortical porosity increased in G and even more in M at week 27. After the diet switch, metabolic and bone cellular disturbances fully reversed in G, but not in M. Trabecular benefit of the obese was preserved in both age groups and in M the age-related bone loss was even lighter after the diet switch than in prolonged HFS. At the diaphysis, cortical porosity normalized in G but not in M. Hypocalcemia in G and M was irreversible. Thus, the mild metabolic syndrome induced by isocaloric HFS is able to alter bone cellular activities and mineral metabolism, reinforce trabecular bone, and affect cortical bone porosity in an irreversible manner in older rats.
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Cédric
authors.initials: C
authors.lastname: Lavet
authors.affiliation: Division of Nephrology, Center for Translational Metabolism and Health Feinberg School of Medicine, Northwestern University, Chicago, IL, USA.
authors.forename: Aline
authors.initials: A
authors.lastname: Martin
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Marie-Thérèse
authors.initials: MT
authors.lastname: Linossier
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Vanden Bossche
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Norbert
authors.initials: N
authors.lastname: Laroche
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Mireille
authors.initials: M
authors.lastname: Thomas
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Maude
authors.initials: M
authors.lastname: Gerbaix
authors.affiliation: Division of Bone Diseases, Department of Internal Medicine Specialties, Geneva University Hospital, Geneva, Switzerland.
authors.forename: Patrick
authors.initials: P
authors.lastname: Ammann
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Antoine
authors.initials: A
authors.lastname: Fraissenon
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Marie-Hélène
authors.initials: MH
authors.lastname: Lafage-Proust
authors.affiliation: Laboratory of Metabolic Adaptations to Exercise in Physiological and Pathological conditions (AME2P, EA3533), Blaise Pascal University, Clermont University, Clermont Ferrand, France.
authors.forename: Daniel
authors.initials: D
authors.lastname: Courteix
authors.affiliation: Institut National de la Santé et de la Recherche Médicale (INSERM) U1059, Laboratoire de Biologie intégrative du Tissu Osseux, Lyon University, Saint-Étienne, France.
authors.forename: Laurence
authors.initials: L
authors.lastname: Vico
mesh_terms: D000375:Aging / Q000378:metabolism* / Q000473:pathology; D000818:Animals; D001853:Bone Marrow / Q000378:metabolism* / Q000473:pathology; D004041:Dietary Fats / Q000009:adverse effects* / Q000494:pharmacology; D006996:Hypocalcemia / Q000139:chemically induced / Q000235:genetics / Q000378:metabolism* / Q000473:pathology; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism; D020780:Matrix Metalloproteinase 9 / Q000235:genetics / Q000378:metabolism; D009765:Obesity / Q000139:chemically induced / Q000378:metabolism* / Q000473:pathology; D051381:Rats; D017208:Rats, Wistar; D013131:Spine / Q000378:metabolism / Q000473:pathology; D013395:Sucrose / Q000009:adverse effects* / Q000494:pharmacology; D013977:Tibia / Q000378:metabolism / Q000473:pathology; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000235:genetics / Q000378:metabolism
chemical_list: D004041:Dietary Fats; C576839:TIMP1 protein, rat; C508962:Tgfb1 protein, rat; D019715:Tissue Inhibitor of Metalloproteinase-1; D053773:Transforming Growth Factor beta1; D013395:Sucrose; D020778:Matrix Metalloproteinase 2; C522363:Mmp2 protein, rat; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
keywords: BONE STRENGTH; CALCIUM-PHOSPHATE METABOLISM; DIABETES; HISTOMORPHOMETRY; OBESITY