Fructose Consumption and Metabolic Dysregulation

Fructose Consumption Aggravates Dysregulation of Postprandial Lipid Metabolism in Obese Hypertriglyceridemic Men With High Cardiometabolic Risk Profile and Associates With Liver Fat Deposition

High fructose intake is increasingly recognized as causative in development of prediabetes, metabolic syndrome and cardiovascular disease (CVD). The mechanisms underlying fructose-induced metabolic disturbances are unclear but are beginning to be unraveled. In contrast to metabolism of glucose, the breakdown of fructose leads to the generation of metabolites that stimulate hepatic de novo lipogenesis (DNL) and increased levels of both fasting and postprandial triglycerides. The key lipogenic transcription factor seems to be activated by fructose independently of insulin. However, it is still controversial whether fructose consumption increases DNL in man to the extent that it induces metabolic disturbances. Animal studies have shown that also the adipose tissue is responsive to fructose feeding fructose, and that high fructose-feeding induces insulin resistance and inflammation in the adipose tissue. The role of intestinal insulin resistance in fructose-induced dysmetabolism has not been studied in detail. The critical question is whether the metabolic disturbances are induced by calorie excess or by fructose per se.

Study Overview

• Status: Completed
• Conditions: Hypertriglyceridemia; Central Obesity
• Intervention / Treatment: Dietary supplement: Fructose

Detailed Description

Detailed description: Study subjects will participate to studies 1-4 before and 3 m after fructose diet:

1. An oral fat load or a kinetic study with stable isotopes combined with an oral fat load.
2. Determination of liver, subcutaneous and intra-abdominal fat. (Proton magnetic resonance spectroscopy )
3. Lipolytic enzymes, advanced lipid analysis, fat biopsies and genetic studies and gut microbiota profiling
4. Oral glucose tolerance test and analysis of incretins and inflammatory biomarkers.

• Study Type: Interventional
• Enrollment (Actual): 82
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Canada
  • Québec, Canada
    • Universite Laval
• Finland
  • Helsinki, Finland, 00290
    • Helsinki University Central Hospital, Biomedicum
• Italy
  • Naples, Italy
    • University of Naples, Federico II, and Faculty of Medicine
• Sweden
  • Gothenburg, Sweden
    • Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 20 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: Male

Description

Inclusion Criteria:

• Body mass index 27-40
• Waist > 96 cm
• Age 20-60 years
• Male

Exclusion Criteria:

• Smoking
• Active health problems
• Contraindications to MRI scanning
• Bleeding tendency
• Abnormal liver or renal function tests
• Type 2 diabetes
• Evidence of metabolic or viral liver disease
• Alcohol intake > 21 units per week
• Chronic medication except ones needed for stable hypertension

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• 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: After fructose feeding; After 3 month fructose diet 75 g/day	Dietary supplement: Fructose; 3 month fructose diet 75 g/day

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
TG Plasma AUC	Before vs. after fructose challenge: Triglycerides (TG) plasma Area Under Curve (AUC)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
B48 Plasma AUC	Before vs. after fructose challenge: apolipoprotein (apo)B48 plasma Area Under Curve (AUC)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
TG Plasma iAUC	Before vs. after fructose challenge:Triglycerides (TG) plasma incremental Area Under Curve (iAUC)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
DNL	Before vs. after fructose challenge: de novo lipogenesis (DNL)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
ApoC-III	Before vs. after fructose challenge: Apolipoprotein C-III (ApoC-III)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
β-OH Butyrate	Before vs. after fructose challenge: beta-OH butyrate (β-OH butyrate)	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Liver Fat	Before vs. after fructose challenge	Form the baseline (time point 1) to end of treatment at 3 months (time point 2)

Collaborators and Investigators

• Sponsor: Marja-Riitta Taskinen
• Collaborators: Lund University; Sahlgrenska University Hospital, Sweden; Laval University; University of Naples
• Investigators: Principal Investigator: Marja-Riitta Taskinen, Professor, Helsinki University Central Hospital, Biomedicum

Publications and helpful links

General Publications

• Taskinen MR, Bjornson E, Matikainen N, Soderlund S, Ramo J, Ainola MM, Hakkarainen A, Sihlbom C, Thorsell A, Andersson L, Bergh PO, Henricsson M, Romeo S, Adiels M, Ripatti S, Laakso M, Packard CJ, Boren J. Postprandial metabolism of apolipoproteins B48, B100, C-III, and E in humans with APOC3 loss-of-function mutations. JCI Insight. 2022 Oct 10;7(19):e160607. doi: 10.1172/jci.insight.160607.

Study record dates

Study Major Dates

• Study Start: August 1, 2011
• Primary Completion (Actual): May 1, 2015
• Study Completion (Actual): June 1, 2015

Study Registration Dates

• First Submitted: September 28, 2011
• First Submitted That Met QC Criteria: September 30, 2011
• First Posted (Estimate): October 4, 2011

Study Record Updates

• Last Update Posted (Actual): June 15, 2021
• Last Update Submitted That Met QC Criteria: May 19, 2021
• Last Verified: May 1, 2021

More Information

Terms related to this study

• Keywords: hypertriglyceridemia; fructose; postprandial lipids; de novo lipogenesis; stable isotopes
• Additional Relevant MeSH Terms: Metabolic Diseases; Overnutrition; Nutrition Disorders; Lipid Metabolism Disorders; Hyperlipidemias; Dyslipidemias; Obesity; Hypertriglyceridemia; Obesity, Abdominal
• Other Study ID Numbers: T1010K0029