Curcuma longa extract associated with white pepper lessens high fat diet-induced inflammation in subcutaneous adipose tissue

Audrey M Neyrinck, Maud Alligier, Patrick B Memvanga, Elodie Névraumont, Yvan Larondelle, Véronique Préat, Patrice D Cani, Nathalie M Delzenne, Audrey M Neyrinck, Maud Alligier, Patrick B Memvanga, Elodie Névraumont, Yvan Larondelle, Véronique Préat, Patrice D Cani, Nathalie M Delzenne

Abstract

Background: Supra-nutritional doses of curcumin, derived from the spice Curcuma longa, have been proposed as a potential treatment of inflammation and metabolic disorders related to obesity. The aim of the present study was to test whether Curcuma longa extract rich in curcumin and associated with white pepper (Curcuma-P®), at doses compatible with human use, could modulate systemic inflammation in diet-induced obese mice. We questioned the potential relevance of changes in adiposity and gut microbiota in the effect of Curcuma-P® in obesity.

Methodology/principal findings: Mice were fed either a control diet (CT), a high fat (HF) diet or a HF diet containing Curcuma longa extract (0.1 % of curcumin in the HF diet) associated with white pepper (0.01 %) for four weeks. Curcumin has been usually combined with white pepper, which contain piperine, in order to improve its bioavailability. This combination did not significantly modify body weight gain, glycemia, insulinemia, serum lipids and intestinal inflammatory markers. Tetrahydrocurcumin, but not curcumin accumulated in the subcutaneous adipose tissue. Importantly, the co-supplementation in curcuma extract and white pepper decreased HF-induced pro-inflammatory cytokines expression in the subcutaneous adipose tissue, an effect independent of adiposity, immune cells recruitment, angiogenesis, or modulation of gut bacteria controlling inflammation.

Conclusions/significance: These findings support that nutritional doses of Curcuma longa, associated with white pepper, is able to decrease inflammatory cytokines expression in the adipose tissue and this effect could be rather linked to a direct effect of bioactive metabolites reaching the adipose tissue, than from changes in the gut microbiota composition.

Conflict of interest statement

Competing Interests: This study was funded by Longévie SA. There are no patents, products in development or marketed products to declare. This does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials, as detailed online in the guide for authors.

Figures

Figure 1. Body weight and body composition.
Figure 1. Body weight and body composition.
Body weight evolution (A), body weight gain (B), fat mass evolution (C) and lean mass evolution (D) of mice fed a control diet (CT), a high fat diet (HF) or a high fat diet supplemented with Curcuma-P® (HF-CC) for 4 weeks. Data with different superscript letters are significantly different at p

Figure 2. mRNA levels of key markers…

Figure 2. mRNA levels of key markers in subcutaneous adipose tissue.

Mice were fed a…

Figure 2. mRNA levels of key markers in subcutaneous adipose tissue.
Mice were fed a high fat diet (HF) or a high fat diet supplemented with Curcuma-P® (HF-CC) for 4 weeks. Values are expressed relative to controls (set at 1). Data with different superscript letters are significantly different at p

Figure 3. Bacterial quantification per total caecal…

Figure 3. Bacterial quantification per total caecal content.

Caecal bacterial content of total bacteria (A),…

Figure 3. Bacterial quantification per total caecal content.
Caecal bacterial content of total bacteria (A), Bacteroides-Prevotella spp. (B), Bifidobacterium spp. (C), Lactobacillus spp. (D). Bacterial quantities are expressed as Log10 (bacterial cells/caecal content wet weight). Mice were fed a high fat diet (HF) or a high fat diet supplemented with Curcuma-P® (HF-CC) for 4 weeks. ANOVA test, p>0.05.
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P.D. Cani is Research Associate from the FRS-FNRS (Fonds de la Recherche Scientifique, http://www.frs-fnrs.be/), Belgium. M. Alligier is the recipient of a grant from the SFD (Société Francophone du Diabète). This work was supported by Longévie SA. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.
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Figure 2. mRNA levels of key markers…
Figure 2. mRNA levels of key markers in subcutaneous adipose tissue.
Mice were fed a high fat diet (HF) or a high fat diet supplemented with Curcuma-P® (HF-CC) for 4 weeks. Values are expressed relative to controls (set at 1). Data with different superscript letters are significantly different at p

Figure 3. Bacterial quantification per total caecal…

Figure 3. Bacterial quantification per total caecal content.

Caecal bacterial content of total bacteria (A),…

Figure 3. Bacterial quantification per total caecal content.
Caecal bacterial content of total bacteria (A), Bacteroides-Prevotella spp. (B), Bifidobacterium spp. (C), Lactobacillus spp. (D). Bacterial quantities are expressed as Log10 (bacterial cells/caecal content wet weight). Mice were fed a high fat diet (HF) or a high fat diet supplemented with Curcuma-P® (HF-CC) for 4 weeks. ANOVA test, p>0.05.
Figure 3. Bacterial quantification per total caecal…
Figure 3. Bacterial quantification per total caecal content.
Caecal bacterial content of total bacteria (A), Bacteroides-Prevotella spp. (B), Bifidobacterium spp. (C), Lactobacillus spp. (D). Bacterial quantities are expressed as Log10 (bacterial cells/caecal content wet weight). Mice were fed a high fat diet (HF) or a high fat diet supplemented with Curcuma-P® (HF-CC) for 4 weeks. ANOVA test, p>0.05.

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