We hypothesize that the metabolic effects of acute infusion of acetate are different in insulin resistant subjects compared to lean subjects.
ID
Bron
Verkorte titel
Aandoening
metabolic syndrome
Ondersteuning
Onderzoeksproduct en/of interventie
Uitkomstmaten
Primaire uitkomstmaten
The main objective of this study is to look at the effect of iv acetate infusion on postprandial glucose metabolism and whether this effect differs between healthy lean subjects and obese subjects with metabolic syndrome.
Achtergrond van het onderzoek
Obesity is a major public health problem. Mounting evidence suggest a prominent role for the gut microbiome in pathophysiological pathways that influence the central nervous system (CNS) regulation of food intake. In this regard, the short-chain fatty acid (SCFA) acetate is one of the major metabolites produced by gut microbiota from dietary fibre. It has been established that acetate is absorbed into the blood stream and passes the blood brain barrier (BBB). In rodent studies, acetate has been shown to function as a beneficial substrate in hypothalamic brain regions to mediate both glucose metabolism and insulin secretion as central appetite regulation. However, certain other studies have shown contradicting results thus leaving the role of acetate in energy metabolism and appetite regulation controversial. Moreover, the metabolic effects of acetate may be different in insulin resistant subjects compared to the physiological situation. We therefore aim to study the acute effects of intravenous (iv) infusion of acetate on glucose metabolism and CNS regulation of food intake both in healthy lean subjects and in obese subjects with metabolic syndrome.
Doel van het onderzoek
We hypothesize that the metabolic effects of acute infusion of acetate are different in insulin resistant subjects compared to lean subjects.
Onderzoeksopzet
Differences in postprandial plasma glucose and insulin will be compared between the acetate intervention and placebo condition by means of a 120min SMMT after either acetate or saline infusion
Onderzoeksproduct en/of interventie
intravenous infusion of acetate or saline
Publiek
Wetenschappelijk
Belangrijkste voorwaarden om deel te mogen nemen (Inclusiecriteria)
Inclusion criteria healthy lean subject group:
- Healthy Caucasian male or female
- Age 40-65
- Women must be post-menopausal
- BMI range of 19-25 kg/m2
- Subjects should be able and willing to give informed consent.
Inclusion criteria obese metabolic syndrome subject group:
- Caucasian male or female with metabolic syndrome
- Age 40-65
- Women must be post-menopausal
- BMI range of 25-40 kg/m2
- At least 3 out of 5 NCEP metabolic syndrome criteria: fasting plasma glucose ≥ 5.6 mmol/L and/or HOMA-IR ≥ 2.5, triglycerides ≥ 1.6 mmol/L, waist-circumference > 102 cm, HDL cholesterol ≤ 1.04 mmol/L, blood pressure ≥ 130/85.
- Subjects should be able and willing to give informed consent.
Belangrijkste redenen om niet deel te kunnen nemen (Exclusiecriteria)
Exclusion criteria for all participants
- Systemic medication use, except for paracetamol
- Oral or intravenous antibiotics in the past 3 months before inclusion
- Smoking
- Substance abuse
- Contra-indication for MRI, such as claustrophobia or pacemaker
Opzet
Deelname
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In overige registers
Register | ID |
---|---|
NTR-new | NL8381 |
Ander register | METC AMC : METC 2019_211 |