Impact of FTO Gene Variation on Body Composition, Lipid Profile, Insulin Resistance, Advanced Glycation End-Products and Ghrelin Levels in Response to Hypocaloric, Protein Rich-Diet

Obesity is a widespread disease that basically develops from unhealthy lifestyle and genetics. The Fat-mass and obesity associated (FTO) gene affects appetite and energy intake of the body, thus elevating fat mass and body weight. The single nucleotide polymorphism (SNP) rs9939609 of the FTO gene is a common variant in different ethnic groups, and its A allele is associated with increased body mass and waist circumference. Hence, the carriers of rs9939609 SNP are prone to weight gain if a healthy diet and lifestyle are not maintained. Similarly, high levels of serum cholesterol and triglycerides, while low levels of high-density lipoproteins are observed in carriers of rs9939609 AA genotype. For individuals having FTO rs9939609 A allele, consumption of hypocaloric diets (1500 kcal/day) consisting of high protein foods up to 25-30% of total daily energy intake might help reduce body weight. However, weight loss tends to vary in individuals after consuming the same diet under similar environmental conditions, so it is important to know the effect of different genotypes that might cause this variation. The study aimed to genotype overweight and obese adults for FTO rs9939609 polymorphism and to determine the effect of this polymorphism on body weight, BMI, waist and hip circumferences, lipid profile, insulin sensitivity, ghrelin levels, inflammatory markers and advanced glycation end-products in these individuals after consumption of a hypocaloric, high-protein diet for 4 weeks.

Study Overview

• Status: Completed
• Conditions: Inflammation; Obesity; Insulin Resistance; Dyslipidemias; Advance Glycation
• Intervention / Treatment: Other: High Protein Low Calorie Dietary Intervention

• Study Type: Interventional
• Enrollment (Actual): 110
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Pakistan
  • KPK
    • Peshawar, KPK, Pakistan, 25100
      • Khyber Medical University
    • Peshawar, KPK, Pakistan, 25100
      • Trial Room Institute of Basic Medical Sciences

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: Adult
• Accepts Healthy Volunteers: Yes

Description

Inclusion Criteria:

• 1Overweight (BMI ≥ 25kg/m2) and obese (BMI ≥ 30kg/m2) individuals.
• Both genders.
• Age 18-50 years.

Exclusion Criteria:

• Children, pregnant and lactating women
• Individuals taking medication for weight loss or undergoing any other weight loss dietary intervention.
• Individuals having lost more than 5 pounds in the past three-month period.
• Patients with any psychiatric disorders, heart, liver, kidney disease, diabetes or abnormal thyroid function.

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Treatment
• Allocation: N/A
• Interventional Model: Single Group Assignment
• Masking: None (Open Label)

Number of Arms

1

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: High Protein Low Calorie Diet; 3 meals/day consumed by the participants with daily caloric intake of 800 kcal. 40-60% of the total calories added from both animal and plant proteins. 30% of the total calories added from fats. 20% of the total calories added from carbohydrates.	Other: High Protein Low Calorie Dietary Intervention; High Protein Diet: Diet consisting of 40-60% total energy from proteins, <20% total energy from carbohydrates and <30% total energy from fats.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Body Composition	Body composition will be measured using Bioimpedance scale which will include percent body fatness, muscle mass, total body water, bone mass and body protein status.	Day 0 and day 29
Lipid Profile	Lipid profile will include concentration of total cholesterol, HDL cholesterol, LDL cholesterol and triglycerides in blood and measured in mg/dl.	Day 0 and day 29
Waist Circumference	Waist circumference will measured in cm using a non-stretchable tape.	Day 0 and day 29
Hip Circumference	Hip circumference will measured in cm using a non-stretchable tape.	Day 0 and day 29
HOMA-IR	HOMA-IR (Homeostatic Model Assessment for Insulin Resistance) will be reported in pmol/L.	Day 0 and day 29
Serum Carboxymethyl lysine levels (CML)	Sreum concentration of Carboxymethyl lysine (CML) will be used an advanced glycation endproduct (AGE) marker and expressed in ng/mL.	Day 0 and day 29
Serum Interleukinin-6 (IL-6)	Serum Interleukinin-6 (IL-6) will be used as marker of inflammation pg/mL.	Day 0 and day 29
Serum Hunger Hormone- Ghrelin	Serum Hunger Hormone- Ghrelin will be used to asses satiety related sensation and expressed as pmol/l.	Day 1(Fasting and postprandial), Day 7(Fasting and postprandial) and Day 28(Fasting and postprandial).
Body Mass Index (BMI)	Body weight will be measured in Kg. Height will be measure in cm. Weight and height will be used to calculate body mass index (BMI) to report in Kg/m^2	Day 0 and day 29
Waist-to-Hip Ratio (WHR)	Waist and Hip Circumference will be measured in cm. These two measures will be used to calculate waist-to-hip ratio (WHR) as waist measurement divided by hip measurement (W⁄H).	Day 0 and Day 29

Collaborators and Investigators

• Sponsor: Khyber Medical University Peshawar

Publications and helpful links

General Publications

• Rexrode KM, Carey VJ, Hennekens CH, Walters EE, Colditz GA, Stampfer MJ, Willett WC, Manson JE. Abdominal adiposity and coronary heart disease in women. JAMA. 1998 Dec 2;280(21):1843-8. doi: 10.1001/jama.280.21.1843.
• Karra E, O'Daly OG, Choudhury AI, Yousseif A, Millership S, Neary MT, Scott WR, Chandarana K, Manning S, Hess ME, Iwakura H, Akamizu T, Millet Q, Gelegen C, Drew ME, Rahman S, Emmanuel JJ, Williams SC, Ruther UU, Bruning JC, Withers DJ, Zelaya FO, Batterham RL. A link between FTO, ghrelin, and impaired brain food-cue responsivity. J Clin Invest. 2013 Aug;123(8):3539-51. doi: 10.1172/JCI44403. Epub 2013 Jul 15.
• McMillan DC, Sattar N, McArdle CS. ABC of obesity. Obesity and cancer. BMJ. 2006 Nov 25;333(7578):1109-11. doi: 10.1136/bmj.39042.565035.BE1. No abstract available.
• Zou ZC, -J Mao L, Shi YY, Chen JH, Wang LS, Cai W. Effect of exercise combined with dietary intervention on obese children and adolescents associated with the FTO rs9939609 polymorphism. Eur Rev Med Pharmacol Sci. 2015 Dec;19(23):4569-75.

Study record dates

Study Major Dates

• Study Start (Actual): May 1, 2024
• Primary Completion (Actual): August 25, 2024
• Study Completion (Actual): August 25, 2024

Study Registration Dates

• First Submitted: May 17, 2024
• First Submitted That Met QC Criteria: May 17, 2024
• First Posted (Actual): May 23, 2024

Study Record Updates

• Last Update Posted (Actual): October 3, 2024
• Last Update Submitted That Met QC Criteria: October 1, 2024
• Last Verified: October 1, 2024

More Information

Terms related to this study

• Keywords: Obesity; Food Intake; Satiety; Interleukin-6; Ghrelin; High protein diet; FTO rs9939609; Carboxymethyl lysine
• Additional Relevant MeSH Terms: Pathologic Processes; Glucose Metabolism Disorders; Metabolic Diseases; Hyperinsulinism; Lipid Metabolism Disorders; Inflammation; Dyslipidemias; Insulin Resistance
• Other Study ID Numbers: KMU/IBMS/IRBE/2023/1209-20

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: NO

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No