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Is Physical Activity, Obesity, and Ethnicity Associated With the Tethering and Migration of Pro-inflammatory Monocytes?

Completed
Conditions
Physical Activity
Central Obesity
Inflammation
Interventions
Behavioral: Habitual physical activity assessment
Registration Number
NCT04761081
Lead Sponsor
Loughborough University
Brief Summary

Being south Asian or centrally obese may be associated with an increased risk of inflammation. The investigators are seeking to investigate whether this is the case by recruiting white European and south Asian men who are lean or have central obesity. Further, the investigators wish to investigate whether physical activity influences the associations.

Detailed Description

Central obesity is associated with an increased risk of cardiovascular disease. Further, south Asians have been shown to be at an increased risk of cardiovascular disease compared to white Europeans.

Cardiovascular disease is underpinned by inflammation. Evidence suggests that people with obesity have a more pro-inflammatory and pro-migratory monocyte profile compared with individuals who are lean. The excessive monocyte migration contributes to metabolic dysfunction over time, increasing the risk of chronic disease. However, there is no evidence in south Asians.

One modifiable risk factor which may be able to influence this is physical inactivity, with higher levels of physical activity being associated with reduced inflammation. However, although south Asians are more at risk of cardiovascular disease than white Europeans, evidence suggests south Asians are also less physically active than white Europeans.

The investigators are looking to recruit south Asian and white European men who are lean or have central obesity to investigate 1) is there an association between ethnicity and the tethering and migration of pro-inflammatory monocytes? 2) is there an association between central obesity and the tethering and migration of pro-inflammatory monocytes, and is there an interaction with ethnicity? 3) do higher levels of physical activity influence the tethering and migration of pro-inflammatory monocytes, and is this influenced by ethnicity or central obesity?

To investigate this, the investigators are looking to recruit south Asian and white European men who are either centrally obese or lean. The investigators require 1 blood sample and the participants to wear an activity monitor for 7 days.

Peripheral blood mononuclear cells (PBMCs) will be isolated from the whole blood sample. Then, the investigators will quantify the migratory capacity of PBMCs to a fixed chemokine gradient over time. Further, the investigators will phenotype the monocytes to indicate the characteristics of the monocytes that migrate towards the chemokine mix.

The activity monitor will quantify habitual physical activity, which will be used in the statistical analyses to investigate whether physical activity may influence the response.

It is important to investigate as it will further scientific knowledge on the underpinnings of chronic disease and enable a better understanding on the role of physical activity to potentially reduce the risk.

Recruitment & Eligibility

Status
COMPLETED
Sex
Male
Target Recruitment
40
Inclusion Criteria
  • Non-smokers (including vaping)
  • Not currently dieting
Exclusion Criteria
  • Musculoskeletal injury that has affected normal ambulation within the last month;
  • Any muscle or bone injuries that influence physical activity
  • Free from heart conditions and blood disorders
  • Weight fluctuation greater than 3kg in the previous 3 months
  • Taking anti-inflammatory medication

Study & Design

Study Type
OBSERVATIONAL
Study Design
Not specified
Arm && Interventions
GroupInterventionDescription
South Asians who are leanHabitual physical activity assessmentThe south Asian group who are lean will be of south Asian ethnicity and a waist circumference \<90cm. The group will receive an accelerometer (Actigraph GT3x) to wear for 7 days to measure habitual physical activity. They will then provide a single blood donation in a fasted state which we will use to quantify the migration of pro-inflammatory monocytes towards adipose tissue specific media. This will then be compared to the other 3 groups to investigate the interaction between ethnicity, central obesity, and physical activity with the migration of pro-inflammatory monocytes. Metabolic markers will be analysed and presented in a participant characteristics table.
South Asians with central obesityHabitual physical activity assessmentThe south Asian group with central obesity will be of south Asian ethnicity and a waist circumference of 90cm or greater. The group will receive an accelerometer (Actigraph GT3x) to wear for 7 days to measure habitual physical activity. They will then provide a single blood donation in a fasted state which we will use to quantify the migration of pro-inflammatory monocytes towards adipose tissue specific media. This will then be compared to the other 3 groups to investigate the interaction between ethnicity, central obesity, and physical activity with the migration of pro-inflammatory monocytes. Metabolic markers will be analysed and presented in a participant characteristics table.
White Europeans who are leanHabitual physical activity assessmentThe white European group who are lean will be of white European ethnicity and a waist circumference \<94cm. The group will receive an accelerometer (Actigraph GT3x) to wear for 7 days to measure habitual physical activity. They will then provide a single blood donation in a fasted state which we will use to quantify the migration of pro-inflammatory monocytes towards adipose tissue specific media. This will then be compared to the other 3 groups to investigate the interaction between ethnicity, central obesity, and physical activity with the migration of pro-inflammatory monocytes. Metabolic markers will be analysed and presented in a participant characteristics table.
White Europeans with central obesityHabitual physical activity assessmentThe white European group with central obesity will be of white European ethnicity and a waist circumference of 94cm or greater. The group will receive an accelerometer (Actigraph GT3x) to wear for 7 days to measure habitual physical activity. They will then provide a single blood donation in a fasted state which we will use to quantify the migration of pro-inflammatory monocytes towards adipose tissue specific media. This will then be compared to the other 3 groups to investigate the interaction between ethnicity, central obesity, and physical activity with the migration of pro-inflammatory monocytes. Metabolic markers will be analysed and presented in a participant characteristics table.
Primary Outcome Measures
NameTimeMethod
Number of classical monocytes that migrated.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of non-classical monocytes that migrated.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Concentrations of classical monocytes.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as cells/uL.

Concentrations of intermediate monocytes.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as cells/uL.

Concentrations of non-classical monocytes.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as cells/uL.

Concentrations of CCR2+ monocytes.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as cells/uL.

Concentrations of CCR2+ classical monocytes.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as cells/uL.

Concentrations of CCR5+ monocytes.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as cells/uL.

Number of intermediate monocytes that migrated.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of intermediate monocytes that tethered.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of non-classical monocytes that tethered.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of CCR5+ monocytes that tethered.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

CCR2+ receptor expression.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry.

Number of monocytes that migrated.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of CCR2+ classical monocytes that migrated.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of monocytes that tethered.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of classical monocytes that tethered.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of CCR2+ classical monocytes that tethered.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of CCR2+ monocytes that migrated.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of CCR5+ monocytes that migrated.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

Number of CCR2+ monocytes that tethered.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry. Presented as number of cells.

CCR5+ receptor expression.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via flow cytometry.

Secondary Outcome Measures
NameTimeMethod
Concentration of triacylglycerol.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of triacylglycerol. Presented as mmol/L.

Concentration of c-reactive protein.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of c-reactive protein. Presented as mg/L.

Concentration of high-density lipoprotein cholesterol (HDL).The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of high-density lipoprotein cholesterol. Presented as mmol/L.

Waist circumferenceThe outcome will be measured as a single-time point assessment in a fasted state on day 1.

Waist circumference. Presented as centimetres.

Systolic blood pressure.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Presented as mmHg.

Diastolic blood pressure.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Presented as mmHg.

Concentration of total cholesterol.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of total cholesterol. Presented as mmol/L.

Concentration of low-density lipoprotein cholesterol (LDL).The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of low-density lipoprotein cholesterol. Presented as mmol/L.

Body fat percentage.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Body fat percentage determined via bioelectrical impedance analysis. Presented as percentage.

Concentration of glucose.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of glucose. Presented as mmol/L.

Concentration of interleukin-6.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of interleukin-6. Presented as pg/mL.

Concentration of non-esterified free fatty acids.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Fasted concentration of non-esterified free fatty acids. Presented as mmol/L.

Lean mass.The outcome will be measured as a single-time point assessment in a fasted state on day 1.

Determined via bioelectrical impedance analysis. Presented in kilograms.

Light physical activity minutes per day.Over 7 days +/- the assessment day

Time spent participating in light physical activity. Presented as minutes per day.

Moderate-to-vigorous activity minutes per day.Over 7 days +/- the assessment day

Time spent participating in moderate-to-vigorous physical activity. Presented as minutes per day.

Daily steps.Over 7 days +/- the assessment day

Total daily steps. Presented as steps per day.

Trial Locations

Locations (1)

National Centre for Sport and Exercise Medicine

šŸ‡¬šŸ‡§

Loughborough, United Kingdom

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