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Clinical Studies and Practice

Lipid stimulation of fatty acid sensors in the human duodenum: relationship with gastrointestinal hormones, BMI and diet

International Journal of Obesity volume 41, pages 233–239 (2017)Cite this article

Subjects

Abstract

Background and aims:

The small intestinal free fatty acid (FFA) sensors, FFA receptor 1 (FFAR1), FFAR4, G-protein receptor 119 (GPR119) and cluster of differentiation-36 (CD36), mediate the fat-induced release of gastrointestinal (GI) hormones. We investigated whether expression of duodenal FFA sensors in humans was (i) altered by intraduodenal (ID) lipid infusion, (ii) disordered in overweight or obese individuals, (iii) related to lipid-induced GI hormone secretion or (iv) affected by habitual dietary patterns.

Methods:

Endoscopic duodenal biopsies were collected from 20 lean (body mass index (BMI): 22±1 kg m−2), 18 overweight (BMI: 27±1 kg m−2) and 19 obese (BMI: 35±1 kg m−2) participants at baseline, and following a 30 min ID Intralipid infusion (2 kcal min−1); FFA sensor expression was quantified by reverse transcription-PCR. On a separate day, participants underwent ID Intralipid infusion (2 kcal min−1) for 120 min, to assess GI hormone responses. Habitual diet was evaluated using food frequency questionnaires.

Results:

Baseline FFAR1 and FFAR4 expression were lower, and CD36 was higher, in obese participants compared with lean participants. ID lipid increased GPR119 and FFAR1 expression equally across study groups, but did not alter FFAR4 or CD36 expression. Increased FFAR1 expression correlated positively with glucose-dependent insulinotropic polypeptide (GIP) secretion (r=0.3, P<0.05), whereas there was no relationship between habitual diet with the expression of FFA sensors.

Conclusions:

Obesity is associated with altered duodenal expression of FFAR1, FFAR4 and CD36, suggesting altered capacity for the sensing, absorption and metabolism, of dietary lipids. GPR119 and FFAR1 are early transcriptional responders to the presence of ID lipid, whereas FFAR1 may be an important trigger for lipid-induced GIP release in humans.

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Acknowledgements

We thank the participants who volunteered their time for this study. We also thank the nursing staff of the Gastrointestinal Investigation Unit at the Royal Adelaide Hospital for assisting with endoscopy studies. We would like to acknowledge biostatistician Kylie Lange for statistical support, Scott Standfield for his work analysing CCK samples and Penelope Fitzgerald for her assistance with participant recruitment and infusion studies. TL was supported by a Career Development Fellowship from the National Health and Medical Research Council of Australia (NHMRC; Grant 1022706, 2012–2018), and CF-B by NHMRC Senior Research Fellowships (Grants 627002, 2010-2015, and 1103020, 2016–2020). This study was supported by funding from the Diabetes Australia Research Trust (Grant Y14G-LITT) and the Royal Adelaide Hospital Research Foundation (Grant 1665). CKR, CF-B, RY and TL acknowledge support from the NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health (Grant 1041687, 2013–17).

Clinical trial registry: This study was prospectively registered with the Australia and New Zealand Clinical Trial Registry (www.anzctr.org.au trial number: ACTRN12612000376842).

Author contributions

TJL conception and design of research; NC, NJI and CKR performed experiments; NC analysed data; NC, TJL, RY and CF-B interpreted results of experiments; NC drafted manuscript and prepared figures; NC, RY, TJL and CF-B edited and revised manuscript. All authors had access to the study data and reviewed and approved the final manuscript.

Disclaimer

A small subset of data from the lean group has been published previously in Clinical Nutrition (doi:10.1016/j.clnu.2016.02.005; Epub ahead of print).

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Authors and Affiliations

  1. Discipline of Medicine, University of Adelaide, Adelaide, SA, Australia

    N Cvijanovic, N J Isaacs, C K Rayner, C Feinle-Bisset, R L Young & T J Little

  2. South Australian Health and Medical Research Institute, Adelaide, SA, Australia

    N Cvijanovic, N J Isaacs & R L Young

  3. NHMRC Centre of Research Excellence in Translating Nutritional Science to Good Health, University of Adelaide, Adelaide, SA, Australia

    N Cvijanovic, C K Rayner, C Feinle-Bisset, R L Young & T J Little

  4. Department of Gastroenterology and Hepatology, Royal Adelaide Hospital, Adelaide, SA, Australia

    C K Rayner & R L Young

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  1. N Cvijanovic
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Correspondence to T J Little.

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Cvijanovic, N., Isaacs, N., Rayner, C. et al. Lipid stimulation of fatty acid sensors in the human duodenum: relationship with gastrointestinal hormones, BMI and diet. Int J Obes 41, 233–239 (2017). https://doi.org/10.1038/ijo.2016.199

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