Study: NCT03038750

Intervention type: OTHER
Intervention: Eligibility and lifestyle restrictions check.
Description: Eligibility will be assessed at each study visit and participants will be informed in advance of their visit.

Intervention type: OTHER
Intervention: Eligibility and lifestyle restrictions check.
Description: Eligibility will be assessed at each study visit and participants will be informed in advance of their visit.

Intervention type: OTHER
Intervention: Eligibility and lifestyle restrictions check.
Description: Eligibility will be assessed at each study visit and participants will be informed in advance of their visit.

Intervention type: OTHER
Intervention: Medical history, demographic and lifestyle factors
Description: Medical History, participants demographics and lifestyle factors will be assessed by the participant completion of the medical history and ethnicity questionnaires.

Intervention type: OTHER
Intervention: Medical history, demographic and lifestyle factors
Description: Medical History, participants demographics and lifestyle factors will be assessed by the participant completion of the medical history and ethnicity questionnaires.

Intervention type: OTHER
Intervention: Medical history, demographic and lifestyle factors
Description: Medical History, participants demographics and lifestyle factors will be assessed by the participant completion of the medical history and ethnicity questionnaires.

Intervention type: OTHER
Intervention: Anthropometric measurements: height, weight, and body fat
Description: Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.

Intervention type: OTHER
Intervention: Anthropometric measurements: height, weight, and body fat
Description: Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.

Intervention type: OTHER
Intervention: Anthropometric measurements: height, weight, and body fat
Description: Height measured by stadiometer. Weight and body fat measured by Tanita scale bioelectrical impedance analysis.

Intervention type: OTHER
Intervention: Blood pressure and heart rate
Description: Parameters will be measured using a validated, automated device while seated and again after 3-5 min standing. All measurements will be done in triplicate.

Intervention type: OTHER
Intervention: Blood pressure and heart rate
Description: Parameters will be measured using a validated, automated device while seated and again after 3-5 min standing. All measurements will be done in triplicate.

Intervention type: OTHER
Intervention: Blood pressure and heart rate
Description: Parameters will be measured using a validated, automated device while seated and again after 3-5 min standing. All measurements will be done in triplicate.

Intervention type: OTHER
Intervention: Forearm blood flow: Visit 1 (EDNRA)
Description: Intra-arterial infusion of Phenylephrine at doses of 0.75, 2.5, and 7.5 μg/min for 6 min each (18 min in total). FBF measured in the last 3 minutes. There will be a 30 minute washout with saline followed by Endothelin-1 infusion of at a dose of 5 pmol/min for 90 min.

Intervention type: OTHER
Intervention: Forearm blood flow: Visit 2 (EDNRA)
Description: Intra-arterial infusion of Sodium nitroprusside infusion at doses of 1, 3, and 10 μg/min for 6 min each (18 min in total). FBF measured in the last 3 minutes. There will be a 20 minute washout with saline followed by infusion of BQ-123 at a dose of 10 nmol/min for 90 min.

Intervention type: OTHER
Intervention: Blood biochemistry (PNPLA3)
Description: 25ml blood will be taken from the participant in a glucose fasting state. Following a high carbohydrate meal, a second 25ml blood sample will be taken. Clinical Biochemistry tests and detailed lipid analysis will be performed.

Intervention type: OTHER
Intervention: Blood EPCR function (PROCR)
Description: Blood sample taken will be analysed via ELISA and FACS.

Intervention type: OTHER
Intervention: Blood platelet coagulation and function (PROCR)
Description: Blood sample taken will be analysed using a Platelet coagulation and function assay.

Intervention type: OTHER
Intervention: Blood endothelial permeability (PROCR)
Description: Blood sample will be analysed in vitro using a permeability assay kit.

Intervention type: OTHER
Intervention: Blood leukocyte-endothelium adhesion (PROCR)
Description: Blood sample will be analysed in vitro using a leukocyte-endothelium adhesion assay.

Intervention type: OTHER
Intervention: Baseline Venepuncture (PNPLA3, Visit 1)
Description: Up to 25ml Blood will be taken.

Intervention type: OTHER
Intervention: Deuterium water - Loading dose 1 (PNPLA3, Visit 1)
Description: Loading dose of 3 g/kg body water.

Intervention type: OTHER
Intervention: Deuterium water - Loading dose 2 (PNPLA3, Visit 1)
Description: Loading dose of 3 g/kg body water.

Intervention type: OTHER
Intervention: Energy-balanced dinner (PNPLA3, Visit 1)
Description: Provided following baseline bloods and loading dose 1.

Intervention type: OTHER
Intervention: Fasting venepuncture (PNPLA3, Visit 2)
Description: Up to 25ml Blood will be taken.

Intervention type: OTHER
Intervention: Deuterium water - Maintenance dose (PNPLA3, Visit 2)
Description: every hour, maintenance dose 0.04 g/kg body water

Intervention type: OTHER
Intervention: Consumption of high carbohydrate meal (PNPLA3, Visit 2)
Description: Provided following fasting blood sample.

Intervention type: OTHER
Intervention: Postprandial Venepuncture (PNPLA3, Visit 2)
Description: Up to 25ml Blood will be taken.

Intervention type: OTHER
Intervention: Venepuncture (PROCR)
Description: Up to 50ml Blood will be taken.