title: Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice.
abstract: Overweight and obesity have become epidemic worldwide and are linked to sedentary lifestyle and the consumption of processed foods and drinks. Citrate is a metabolite that plays central roles in carbohydrate and lipid metabolism. In addition, citrate is the additive most commonly used by the food industry, and therefore is highly consumed. Extracellular citrate can freely enter the cells via the constitutively expressed plasma membrane citrate transporter. Within the cytosol, citrate is readily metabolised by ATP-citrate lyase into acetyl-CoA - the metabolic precursor of endogenously produced lipids and cholesterol. We therefore hypothesised that the citrate ingested from processed foods and drinks could contribute to increased postprandial fat production and weight gain. To test our hypothesis, we administered citrate to mice through their drinking water with or without sucrose and monitored their weight gain and other metabolic parameters. Our results showed that mice receiving citrate or citrate+sucrose did not show increased weight gain or an increase in the weight of the liver, skeletal muscles or adipose tissues (AT). Moreover, the plasma lipid profiles (TAG, total cholesterol, LDL and HDL) were similar across all groups. However, the group receiving citrate+sucrose showed augmented fasting glycaemia, glucose intolerance and the expression of pro-inflammatory cytokines (TNF-α, IL-1β, IL-6 and IL-10) in their AT. Therefore, our results suggest that citrate consumption contributes to increased AT inflammation and altered glucose metabolism, which is indicative of initial insulin resistance. Thus, citrate consumption could be a previously unknown causative agent for the complications associated with obesity.
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: João G B
authors: JG
authors: Leandro
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Jair M
authors: JM
authors: Espindola-Netto
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Maria Carolina F
authors: MC
authors: Vianna
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Lilian S
authors: LS
authors: Gomez
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Thaina M
authors: TM
authors: DeMaria
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Monica M
authors: MM
authors: Marinho-Carvalho
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Patricia
authors: P
authors: Zancan
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Heitor A
authors: HA
authors: Paula Neto
authors: Departamento de Biotecnologia Farmacêutica, Faculdade de Farmácia,Universidade Federal do Rio de Janeiro,Rio de Janeiro, RJ,21941-903,Brazil.
authors: Mauro
authors: http://orcid.org/0000-0001-9796-6829
authors: M
authors: Sola-Penna
mesh_terms: D000818:Animals; D019343:Citric Acid / Q000009:adverse effects*; D016207:Cytokines / Q000097:blood; D066273:Diet, Western / Q000009:adverse effects; D019422:Dietary Sucrose / Q000009:adverse effects*; D005503:Food Additives / Q000009:adverse effects*; D018149:Glucose Intolerance / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D007333:Insulin Resistance; D050152:Intra-Abdominal Fat / Q000276:immunology* / Q000378:metabolism / Q000473:pathology; D008055:Lipids / Q000097:blood; D008099:Liver / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D008297:Male; D051379:Mice; D018482:Muscle, Skeletal / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D009929:Organ Size; D015434:Panniculitis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D011897:Random Allocation
chemical_list: D016207:Cytokines; D019422:Dietary Sucrose; D005503:Food Additives; D008055:Lipids; D019343:Citric Acid
keywords: AT adipose tissues; Citrate; Diabetes; Food additives; GTT glucose tolerance tests; ITT insulin tolerance test; Inflammation; Insulin resistance; Obesity