Skip to main content Accessibility help
×
Home

Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice

  • João G. B. Leandro (a1), Jair M. Espindola-Netto (a1), Maria Carolina F. Vianna (a1), Lilian S. Gomez (a1), Thaina M. DeMaria (a1), Monica M. Marinho-Carvalho (a1), Patricia Zancan (a1), Heitor A. Paula Neto (a1) and Mauro Sola-Penna (a1)...

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.

  • View HTML
    • Send article to Kindle

      To send this article to your Kindle, first ensure no-reply@cambridge.org is added to your Approved Personal Document E-mail List under your Personal Document Settings on the Manage Your Content and Devices page of your Amazon account. Then enter the ‘name’ part of your Kindle email address below. Find out more about sending to your Kindle. Find out more about sending to your Kindle.

      Note you can select to send to either the @free.kindle.com or @kindle.com variations. ‘@free.kindle.com’ emails are free but can only be sent to your device when it is connected to wi-fi. ‘@kindle.com’ emails can be delivered even when you are not connected to wi-fi, but note that service fees apply.

      Find out more about the Kindle Personal Document Service.

      Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice
      Available formats
      ×

      Send article to Dropbox

      To send this article to your Dropbox account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Dropbox.

      Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice
      Available formats
      ×

      Send article to Google Drive

      To send this article to your Google Drive account, please select one or more formats and confirm that you agree to abide by our usage policies. If this is the first time you use this feature, you will be asked to authorise Cambridge Core to connect with your <service> account. Find out more about sending content to Google Drive.

      Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice
      Available formats
      ×

Copyright

Corresponding author

* Corresponding author: Professor M. Sola-Penna, fax +55 21 2280 1784 ext. 231, email maurosp@ufrj.br

References

Hide All
1. Johnson, AR & Makowski, L (2015) Nutrition and metabolic correlates of obesity and inflammation: clinical considerations. J Nutr 145, 1131S1136S.
2. Kelly, T, Yang, W, Chen, CS, et al. (2008) Global burden of obesity in 2005 and projections to 2030. Int J Obes (Lond) 32, 14311437.
3. Popkin, BM, Adair, LS & Ng, SW (2012) Global nutrition transition and the pandemic of obesity in developing countries. Nutr Rev 70, 321.
4. Evans, G, de Challemaison, B & Cox, DN (2010) Consumers’ ratings of the natural and unnatural qualities of foods. Appetite 54, 557563.
5. Chu, KY, Lin, Y, Hendel, A, et al. (2010) ATP-citrate lyase reduction mediates palmitate-induced apoptosis in pancreatic beta cells. J Biol Chem 285, 3260632615.
6. Gameiro, PA, Yang, J, Metelo, AM, et al. (2013) In vivo HIF-mediated reductive carboxylation is regulated by citrate levels and sensitizes VHL-deficient cells to glutamine deprivation. Cell Metab 17, 372385.
7. Chypre, M, Zaidi, N & Smans, K (2012) ATP-citrate lyase: a mini-review. Biochem Biophys Res Commun 422, 14.
8. Ojo, OO, Srinivasan, DK, Owolabi, BO, et al. (2015) Magainin-AM2 improves glucose homeostasis and beta cell function in high-fat fed mice. Biochim Biophys Acta 1850, 8087.
9. Ferreira, AV, Menezes-Garcia, Z, Viana, JB, et al. (2014) Distinct metabolic pathways trigger adipocyte fat accumulation induced by high-carbohydrate and high-fat diets. Nutrition 30, 11381143.
10. Carvalho, BM, Guadagnini, D, Tsukumo, DM, et al. (2012) Modulation of gut microbiota by antibiotics improves insulin signalling in high-fat fed mice. Diabetologia 55, 28232834.
11. Kredel, LI & Siegmund, B (2014) Adipose-tissue and intestinal inflammation – visceral obesity and creeping fat. Front Immunol 5, 462.
12. Esser, N, Legrand-Poels, S, Piette, J, et al. (2014) Inflammation as a link between obesity, metabolic syndrome and type 2 diabetes. Diabetes Res Clin Pract 105, 141150.
13. Labonte, AC, Tosello-Trampont, AC & Hahn, YS (2014) The role of macrophage polarization in infectious and inflammatory diseases. Mol Cells 37, 275285.
14. Iacobazzi, V & Infantino, V (2014) Citrate – new functions for an old metabolite. Biol Chem 395, 387399.
15. Infantino, V, Iacobazzi, V, Palmieri, F, et al. (2013) ATP-citrate lyase is essential for macrophage inflammatory response. Biochem Biophys Res Commun 440, 105111.
16. Palmieri, EM, Spera, I, Menga, A, et al. (2015) Acetylation of human mitochondrial citrate carrier modulates mitochondrial citrate/malate exchange activity to sustain NADPH production during macrophage activation. Biochim Biophys Acta 1847, 729738.
17. Ashbrook, MJ, McDonough, KL, Pituch, JJ, et al. (2015) Citrate modulates lipopolysaccharide-induced monocyte inflammatory responses. Clin Exp Immunol 180, 520530.
18. Shara, M, Ohia, SE, Yasmin, T, et al. (2003) Dose- and time-dependent effects of a novel (-)-hydroxycitric acid extract on body weight, hepatic and testicular lipid peroxidation, DNA fragmentation and histopathological data over a period of 90 days. Mol Cell Biochem 254, 339346.
19. Asghar, M, Monjok, E, Kouamou, G, et al. (2007) Super CitriMax (HCA-SX) attenuates increases in oxidative stress, inflammation, insulin resistance, and body weight in developing obese Zucker rats. Mol Cell Biochem 304, 9399.

Keywords

Exogenous citrate impairs glucose tolerance and promotes visceral adipose tissue inflammation in mice

  • João G. B. Leandro (a1), Jair M. Espindola-Netto (a1), Maria Carolina F. Vianna (a1), Lilian S. Gomez (a1), Thaina M. DeMaria (a1), Monica M. Marinho-Carvalho (a1), Patricia Zancan (a1), Heitor A. Paula Neto (a1) and Mauro Sola-Penna (a1)...

Metrics

Altmetric attention score

Full text views

Total number of HTML views: 0
Total number of PDF views: 0 *
Loading metrics...

Abstract views

Total abstract views: 0 *
Loading metrics...

* Views captured on Cambridge Core between <date>. This data will be updated every 24 hours.

Usage data cannot currently be displayed