title: Excess fructose intake-induced hypertrophic visceral adipose tissue results from unbalanced precursor cell adipogenic signals.
abstract: We studied the effect of feeding normal adult male rats with a commercial diet supplemented with fructose added to the drinking water (10% w/v; fructose-rich diet, FRD) on the adipogenic capacity of stromal-vascular fraction (SVF) cells isolated from visceral adipose tissue (VAT) pads. Animals received either the commercial diet or FRD ad libitum for 3 weeks; thereafter, we evaluated the in vitro proliferative and adipogenic capacities of their VAT SVF cells. FRD significantly increased plasma insulin, triglyceride and leptin levels, VAT mass/cell size, and the in vitro adipogenic capacity of SVF cells. Flow cytometry studies indicated that the VAT precursor cell population number did not differ between groups; however, the accelerated adipogenic process could result from an imbalance between endogenous pro- and anti-adipogenic SVF cell signals, which are clearly shifted towards the former. The increased insulin milieu and its intracellular mediator (insulin receptor substrate-1) in VAT pads, as well as the enhanced SVF cell expression of Zpf423 and peroxisome proliferator receptor-γ2 (all pro-adipogenic modulators), together with a decreased SVF cell concentration of anti-adipogenic factors (pre-adipocyte factor-1 and wingless-type MMTV-10b), strongly supports this assumption. We hypothesize that the VAT mass expansion recorded in FRD rats results from the combination of initial accelerated adipogenesis and final cell hypertrophy. It remains to be determined whether FRD administration over longer periods could perpetuate both processes, or whether cell hypertrophy itself remains responsible for a further VAT mass expansion, as observed in advanced/morbid obesity.
authors.affiliation: IMBICE - Instituto Multidisciplinario de Biología Celular, Neuroendocrine Unit (CICPBA-CONICET LA PLATA), Argentina.
authors.forename: María G
authors.initials: MG
authors.lastname: Zubiría
authors.forename: Juan P
authors.initials: JP
authors.lastname: Fariña
authors.forename: Griselda
authors.initials: G
authors.lastname: Moreno
authors.forename: Juan J
authors.initials: JJ
authors.lastname: Gagliardino
authors.forename: Eduardo
authors.initials: E
authors.lastname: Spinedi
authors.forename: Andrés
authors.initials: A
authors.lastname: Giovambattista
mesh_terms: D017667:Adipocytes / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D050156:Adipogenesis / Q000187:drug effects* / Q000502:physiology; D054392:Adipokines / Q000235:genetics / Q000378:metabolism; D000818:Animals; D049108:Cell Enlargement / Q000187:drug effects; D049109:Cell Proliferation / Q000187:drug effects; D004040:Dietary Carbohydrates / Q000008:administration & dosage* / Q000633:toxicity; D005632:Fructose / Q000008:administration & dosage* / Q000633:toxicity; D050152:Intra-Abdominal Fat / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology*; D008297:Male; D047495:PPAR gamma / Q000235:genetics / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015398:Signal Transduction / Q000187:drug effects; D017154:Stromal Cells / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D013549:Sweetening Agents / Q000008:administration & dosage / Q000633:toxicity
chemical_list: D054392:Adipokines; D004040:Dietary Carbohydrates; D047495:PPAR gamma; D013549:Sweetening Agents; D005632:Fructose
keywords: SVF cells; abdominal adipose tissue; adipogenic factors; leptin; lipid