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.

Detailed description: Study subjects will participate to studies 1-4 before and 3 m after fructose diet: An oral fat load or a kinetic study with stable isotopes combined with an oral fat load. Determination of liver, subcutaneous and intra-abdominal fat. (Proton magnetic resonance spectroscopy ) Lipolytic enzymes, advanced lipid analysis, fat biopsies and genetic studies and gut microbiota profiling Oral glucose tolerance test and analysis of incretins and inflammatory biomarkers.

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

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.