High-fat Overfeeding, Hepatokines and Appetite Regulation

NCT03369145 | Completed

• 1 other identifier: R17-P144
• Study Type: interventional
• Target: 12
• Locations: 1 country
• Sites: 2

Brief Summary

The present study will investigate the effect of high-fat overfeeding on a group of liver-secreted proteins linked to worsened blood sugar control, as well as proteins involved in appetite control. Participants will consume both a high-fat diet, consisting of 50% extra calories above their daily required intake, and a control diet, consisting of their normal 'habitual' diet, with each diet lasting seven days. The diets will be undertaken in a randomised order, with a period of three weeks separating the two diets. Blood samples will be taken before and after each diet to measure blood sugar control. Further blood samples will also be taken 24 hours and 72 hours into each diet to see how levels of the liver and appetite-regulating proteins change over the course of the seven days. It is expected that blood sugar control will be worsened by the high-fat diet and this will be accompanied by increases in levels of the liver-secreted proteins and an impaired release of the appetite-regulating proteins into the blood.

Conditions

Insulin Resistance; Type2 Diabetes Mellitus; Non-Alcoholic Fatty Liver Disease; Obesity

Keywords

Hepatokines; High Fat Diet; Glycaemic Control; Fibroblast Growth Factor 21; Leukocyte Cell-derived Chemotaxin 2; Fetuin-A; Appetite; Ghrelin; Peptide YY

Outcome Measures

Primary Outcomes (1)

• Leukocyte cell-derived chemotaxin 2 (LECT2)

  Time-course of LECT2 plasma concentrations across the 7-day dietary interventions

  Baseline, 1 day, 3 days, 7 days

Secondary Outcomes (17)

• Fibroblast growth factor 21 (FGF21)

  Baseline, 1 day, 3 days, 7 days

• Fetuin-A

  Baseline, 1 day, 3 days, 7 days

• Acylated ghrelin

  Baseline, 1 day, 3 days, 7 days

• Peptide YY (PYY)

  Baseline, 1 day, 3 days, 7 days

• C-Terminal Telopeptide of Type 1 Collagen (CTX)

  Baseline, 1 day, 3 days, 7 days

Study Arms (2)

High-fat diet

EXPERIMENTAL

Participants will consume a hypercaloric, high-fat diet. Participants will be provided with all the food during the week and will be instructed to consume all of the foods provided and no extra calorie containing food or drink. In the event of leftover food, participants will be asked to return the food for measurement and subsequent subtraction from their total energy intake.

Dietary Supplement: High-fat diet

Control diet

NO INTERVENTION

Participants will consume their normal 'habitual' diet for seven days which will be compared to their habitual diet recorded by a three day food diary before commencing the two diets. Participants will be instructed to carry on as normal and eat their usual diet and this period will be used as a comparator to the high-fat diet. They will also be told to record their food intake for 3 days during the diet to quantify their control diet.

Interventions

High-fat diet DIETARY_SUPPLEMENT

The high-fat diet will provide 7 days of overfeeding comprising of: +50% extra calories above the daily required intake, 65% of which is fat.

High-fat diet

Eligibility Criteria

• Age: 18 Years - 40 Years
• Sex: male
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64)

You may qualify if:

• Recreationally active - ≤ 2 structured exercise sessions per week
• BMI between 18.5 - 27.9 kg/m2
• Body fat percentage \< 20%
• Metabolically healthy - No known cardiovascular or metabolic disease such as diabetes, respiratory or heart disease.
• Non-smoker
• Weight stable in the past 6 months
• Normal fasting blood glucose levels (3.6 - 5.5 mmol/l)

You may not qualify if:

• Contraindications to exercise
• Needle Phobia

Sponsors & Collaborators

• Loughborough University: lead
• Nottingham Trent University: collaborator
• Nottingham University Hospitals NHS Trust: collaborator

Study Sites (2)

National Centre for Sport and Exercise Medicine, Loughborough University

Loughborough, Leicestershire, LE11 3TU, United Kingdom

Location

Clifton Campus, Nottingham Trent University

Nottingham, Nottinghamshire, NG1 4FQ, United Kingdom

Location

Related Publications (10)

• Badman MK, Pissios P, Kennedy AR, Koukos G, Flier JS, Maratos-Flier E. Hepatic fibroblast growth factor 21 is regulated by PPARalpha and is a key mediator of hepatic lipid metabolism in ketotic states. Cell Metab. 2007 Jun;5(6):426-37. doi: 10.1016/j.cmet.2007.05.002.

  PMID: 17550778 BACKGROUND

• Dasgupta S, Bhattacharya S, Biswas A, Majumdar SS, Mukhopadhyay S, Ray S, Bhattacharya S. NF-kappaB mediates lipid-induced fetuin-A expression in hepatocytes that impairs adipocyte function effecting insulin resistance. Biochem J. 2010 Aug 1;429(3):451-62. doi: 10.1042/BJ20100330.

  PMID: 20482516 BACKGROUND

• Groop LC. Insulin resistance: the fundamental trigger of type 2 diabetes. Diabetes Obes Metab. 1999 May;1 Suppl 1:S1-7. doi: 10.1046/j.1463-1326.1999.0010s1001.x.

  PMID: 11220283 BACKGROUND

• Hulston CJ, Churnside AA, Venables MC. Probiotic supplementation prevents high-fat, overfeeding-induced insulin resistance in human subjects. Br J Nutr. 2015 Feb 28;113(4):596-602. doi: 10.1017/S0007114514004097. Epub 2015 Jan 29.

  PMID: 25630516 BACKGROUND

• Lan F, Misu H, Chikamoto K, Takayama H, Kikuchi A, Mohri K, Takata N, Hayashi H, Matsuzawa-Nagata N, Takeshita Y, Noda H, Matsumoto Y, Ota T, Nagano T, Nakagen M, Miyamoto K, Takatsuki K, Seo T, Iwayama K, Tokuyama K, Matsugo S, Tang H, Saito Y, Yamagoe S, Kaneko S, Takamura T. LECT2 functions as a hepatokine that links obesity to skeletal muscle insulin resistance. Diabetes. 2014 May;63(5):1649-64. doi: 10.2337/db13-0728. Epub 2014 Jan 29.

  PMID: 24478397 BACKGROUND

• Meex RCR, Watt MJ. Hepatokines: linking nonalcoholic fatty liver disease and insulin resistance. Nat Rev Endocrinol. 2017 Sep;13(9):509-520. doi: 10.1038/nrendo.2017.56. Epub 2017 Jun 9.

  PMID: 28621339 BACKGROUND

• Parry SA, Smith JR, Corbett TR, Woods RM, Hulston CJ. Short-term, high-fat overfeeding impairs glycaemic control but does not alter gut hormone responses to a mixed meal tolerance test in healthy, normal-weight individuals. Br J Nutr. 2017 Jan;117(1):48-55. doi: 10.1017/S0007114516004475. Epub 2017 Jan 24.

  PMID: 28115026 BACKGROUND

• Uebanso T, Taketani Y, Yamamoto H, Amo K, Ominami H, Arai H, Takei Y, Masuda M, Tanimura A, Harada N, Yamanaka-Okumura H, Takeda E. Paradoxical regulation of human FGF21 by both fasting and feeding signals: is FGF21 a nutritional adaptation factor? PLoS One. 2011;6(8):e22976. doi: 10.1371/journal.pone.0022976. Epub 2011 Aug 1.

  PMID: 21829679 BACKGROUND

• Lean ME, Malkova D. Altered gut and adipose tissue hormones in overweight and obese individuals: cause or consequence? Int J Obes (Lond). 2016 Apr;40(4):622-32. doi: 10.1038/ijo.2015.220. Epub 2015 Oct 26.

  PMID: 26499438 BACKGROUND

• Willis SA, Sargeant JA, Yates T, Takamura T, Takayama H, Gupta V, Brittain E, Crawford J, Parry SA, Thackray AE, Varela-Mato V, Stensel DJ, Woods RM, Hulston CJ, Aithal GP, King JA. Acute Hyperenergetic, High-Fat Feeding Increases Circulating FGF21, LECT2, and Fetuin-A in Healthy Men. J Nutr. 2020 May 1;150(5):1076-1085. doi: 10.1093/jn/nxz333.

  PMID: 31919514 DERIVED

MeSH Terms

Conditions

Insulin Resistance; Non-alcoholic Fatty Liver Disease; Obesity

Interventions

Diet, High-Fat

Condition Hierarchy (Ancestors)

Hyperinsulinism; Glucose Metabolism Disorders; Metabolic Diseases; Nutritional and Metabolic Diseases; Fatty Liver; Liver Diseases; Digestive System Diseases; Overweight; Overnutrition; Nutrition Disorders; Body Weight; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Intervention Hierarchy (Ancestors)

Diet; Nutritional Physiological Phenomena; Diet, Food, and Nutrition; Physiological Phenomena

Study Officials

• James A King, PhD

  Loughborough University

  PRINCIPAL INVESTIGATOR

• Scott A Willis, MSc

  Loughborough University

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: RANDOMIZED
• Masking: NONE
• Purpose: BASIC SCIENCE
• Intervention Model: CROSSOVER
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Principal Investigator

Model Details: The study design is a randomised, controlled, crossover design in which participants undertake two 7-day dietary conditions in a randomised order with a three week washout period in between.

Study Record Dates

• First Submitted: November 20, 2017
• First Posted: December 11, 2017
• Study Start: December 11, 2017
• Primary Completion: July 31, 2018
• Study Completion: July 31, 2018
• Last Updated: February 18, 2019

Record last verified: 2019-02

Locations

GB (2)