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

Sponsor

Loughborough University (Other)

Overall Status

Completed

CT.gov ID

NCT04761081

Collaborator

(none)

Enrollment

Location

11.1

Actual Duration (Months)

3.6

Patients Per Site Per Month

Study Details

Study Description

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.

Condition or Disease	Intervention/Treatment	Phase
Physical Activity Central Obesity Inflammation	Behavioral: Habitual physical activity assessment

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.

Study Design

Study Type:

Observational

Actual Enrollment :

40 participants

Observational Model:

Case-Control

Time Perspective:

Cross-Sectional

Official Title:

Is Physical Activity Associated With the Tethering and Migration of Pro-inflammatory Monocytes in White European and South Asian Males With and Without Central Obesity.

Actual Study Start Date :

Mar 1, 2021

Actual Primary Completion Date :

Aug 1, 2021

Actual Study Completion Date :

Feb 1, 2022

Arms and Interventions

Arm	Intervention/Treatment
South Asians who are lean The 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.	Behavioral: Habitual physical activity assessment 7 days habitual physical activity via accelerometry (ActiGraph GT3x). Specifically steps per day, light physical activity (minutes per day), and moderate to vigorous physical activity (minutes per day).
South Asians with central obesity The 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.	Behavioral: Habitual physical activity assessment 7 days habitual physical activity via accelerometry (ActiGraph GT3x). Specifically steps per day, light physical activity (minutes per day), and moderate to vigorous physical activity (minutes per day).
White Europeans who are lean The 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.	Behavioral: Habitual physical activity assessment 7 days habitual physical activity via accelerometry (ActiGraph GT3x). Specifically steps per day, light physical activity (minutes per day), and moderate to vigorous physical activity (minutes per day).
White Europeans with central obesity The 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.	Behavioral: Habitual physical activity assessment 7 days habitual physical activity via accelerometry (ActiGraph GT3x). Specifically steps per day, light physical activity (minutes per day), and moderate to vigorous physical activity (minutes per day).

Outcome Measures

Primary Outcome Measures

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 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 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 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 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.
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 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 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 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 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 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.
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 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.
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

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 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.
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.
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 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 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 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.
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.
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.
Waist circumference [The 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.
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.

Eligibility Criteria

Criteria

Ages Eligible for Study:

18 Years to 60 Years

Sexes Eligible for Study:

Male

Accepts Healthy Volunteers:

Yes

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