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

Study Overview
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Brief Summary
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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
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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.

Official Title
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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.

Conditions
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Physical Activity, Central Obesity, Inflammation

Intervention / Treatment
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* Behavioral: Habitual physical activity assessment


Participation Criteria
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Eligibility Criteria
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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

Ages Eligible for Study
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Minimum Age: 18 Years
Maximum Age: 60 Years

Sexes Eligible for Study
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Male

Accepts Healthy Volunteers
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Accepts Healthy Volunteers

Study Plan
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How is the study designed?
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Arms and Interventions

| Participant Group/Arm | Intervention/Treatment |
| --- | --- |
| South Asians who are lean<br>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<br>* 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).<br>|
| South Asians with central obesity<br>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<br>* 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).<br>|
| White Europeans who are lean<br>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<br>* 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).<br>|
| White Europeans with central obesity<br>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<br>* 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).<br>|

What is the study measuring?
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Primary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentrations of classical monocytes. | Determined via flow cytometry. Presented as cells/uL. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentrations of intermediate monocytes. | Determined via flow cytometry. Presented as cells/uL. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentrations of non-classical monocytes. | Determined via flow cytometry. Presented as cells/uL. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentrations of CCR2+ monocytes. | Determined via flow cytometry. Presented as cells/uL. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentrations of CCR2+ classical monocytes. | Determined via flow cytometry. Presented as cells/uL. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentrations of CCR5+ monocytes. | Determined via flow cytometry. Presented as cells/uL. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of monocytes that migrated. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of classical monocytes that migrated. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of intermediate monocytes that migrated. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of non-classical monocytes that migrated. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of CCR2+ monocytes that migrated. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of CCR2+ classical monocytes that migrated. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of CCR5+ monocytes that migrated. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of monocytes that tethered. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of classical monocytes that tethered. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of intermediate monocytes that tethered. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of non-classical monocytes that tethered. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of CCR2+ monocytes that tethered. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of CCR2+ classical monocytes that tethered. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Number of CCR5+ monocytes that tethered. | Determined via flow cytometry. Presented as number of cells. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| CCR2+ receptor expression. | Determined via flow cytometry. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| CCR5+ receptor expression. | Determined via flow cytometry. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 

Secondary Outcome Measures

| Outcome Measure | Measure Description | Time Frame |
| --- | --- | --- |
| Concentration of total cholesterol. | Fasted concentration of total cholesterol. Presented as mmol/L. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentration of high-density lipoprotein cholesterol (HDL). | Fasted concentration of high-density lipoprotein cholesterol. Presented as mmol/L. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentration of low-density lipoprotein cholesterol (LDL). | Fasted concentration of low-density lipoprotein cholesterol. Presented as mmol/L. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentration of triacylglycerol. | Fasted concentration of triacylglycerol. Presented as mmol/L. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentration of glucose. | Fasted concentration of glucose. Presented as mmol/L. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentration of c-reactive protein. | Fasted concentration of c-reactive protein. Presented as mg/L. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentration of interleukin-6. | Fasted concentration of interleukin-6. Presented as pg/mL. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Concentration of non-esterified free fatty acids. | Fasted concentration of non-esterified free fatty acids. Presented as mmol/L. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Body fat percentage. | Body fat percentage determined via bioelectrical impedance analysis. Presented as percentage. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Lean mass. | Determined via bioelectrical impedance analysis. Presented in kilograms. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Waist circumference | Waist circumference. Presented as centimetres. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Systolic blood pressure. | Presented as mmHg. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Diastolic blood pressure. | Presented as mmHg. | The outcome will be measured as a single-time point assessment in a fasted state on day 1. | 
| Light physical activity minutes per day. | Time spent participating in light physical activity. Presented as minutes per day. | Over 7 days +/- the assessment day | 
| Moderate-to-vigorous activity minutes per day. | Time spent participating in moderate-to-vigorous physical activity. Presented as minutes per day. | Over 7 days +/- the assessment day | 
| Daily steps. | Total daily steps. Presented as steps per day. | Over 7 days +/- the assessment day | 

 Terms related to the study
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Keywords Provided by Centre Hospitalier Valida
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Physical activity, Central obesity, Ethnicity, Inflammation