Clinical trial NCT01445730: Fructose Consumption and Metabolic Dysregulation
Official title: Fructose Consumption Aggravates Dysregulation of Postprandial Lipid Metabolism in Obese Hypertriglyceridemic Men With High Cardiometabolic Risk Profile and Associates With Liver Fat Deposition
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Central Obesity
Hypertriglyceridemia
Keywords: fructose
hypertriglyceridemia
postprandial lipids
de novo lipogenesis
stable isotopes
Lead sponsor: Helsinki University Central Hospital
Sponsor class: OTHER
Collaborators: name: Sahlgrenska University Hospital
name: Lund University
name: University of Naples
name: Laval University
First posted: 2011-10-04
Enrollment: 82
Sex: MALE
Minimum age (years): 20
Maximum age (years): 60
Standard ages: ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Primary purpose: BASIC_SCIENCE

Brief summary: 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.

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.

Eligibility criteria: 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

Primary outcomes:
measure: TG Plasma AUC
timeFrame: Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
measure: B48 Plasma AUC
timeFrame: Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
measure: TG Plasma iAUC
timeFrame: Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Secondary outcomes:
measure: DNL
timeFrame: Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
measure: ApoC-III
timeFrame: Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
measure: β-OH Butyrate
timeFrame: Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
measure: Liver Fat
timeFrame: Form the baseline (time point 1) to end of treatment at 3 months (time point 2)
Other outcomes:
Locations:
city: Québec
country: Canada
facility: Université Laval
city: Helsinki
country: Finland
facility: Helsinki University Central Hospital, Biomedicum
city: Naples
country: Italy
facility: University of Naples, Federico II, and Faculty of Medicine
city: Gothenburg
country: Sweden
facility: Sahlgrenska Academy at University of Gothenburg and Sahlgrenska University Hospital
Study officials:
affiliation: Helsinki University Central Hospital, Biomedicum
name: Marja-Riitta Taskinen, Professor
role: PRINCIPAL_INVESTIGATOR
References:
citation: 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.