The primary objective of this study is to determine the association between DNL and hepatic %SFA in overweight/obese subjects differing in liver fat content. The secondary objectives are to determine the association between adipose tissue fat…
ID
Source
Brief title
Condition
- Hepatic and hepatobiliary disorders
- Glucose metabolism disorders (incl diabetes mellitus)
Synonym
Research involving
Sponsors and support
Intervention
Outcome measures
Primary outcome
- %SFA expressed as relative amount of SFA to the total amount of fatty
acids.
- DNL expressed as percentage of palmitate in very-low-density-lipoprotein
(VLDL)-TG originating from DNL
Secondary outcome
- Liver fat composition expressed as relative amount of MUFA and PUFA to the
total amount of fatty acids, in addition to %SFA
- Adipose tissue fat composition expressed as relative amount of SFA, MUFA and
PUFA to the total amount of fatty acids
- Adipose tissue fat composition expressed as relative amount of linoleic acid,
docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA) to the total amount
of fatty acids.
- Hepatic, peripheral and whole body insulin sensitivity expressed as %
suppression of endogenous glucose production (EGP), rate of disappearance (Rd)
in *mol/kg/min and glucose infusion rate (GIR) in *mol/kg/min.
- Muscle insulin sensitivity expressed as determinants/markers for muscle
insulin sensitivity in muscle biopsy (oxphos, GLUT4, intramyocellular lipids
(IMCL).
Background summary
Excessive fat in the liver, in absence of high alcohol consumption, is
diagnosed as non-alcoholic fatty liver (NAFL). NAFL prevalence is as high as
50-70% in obese people and is associated with impairments in metabolic health,
e.g. insulin resistance. Not only the amount, but also the composition of the
fat stored in the liver appears to be linked to health outcome measures, such
as insulin resistance, but this evidence comes mainly from animal studies.
Since fat composition has been linked to health outcome measures, it is
important to understand what determines the fatty acid composition of liver
fat. De novo lipogenesis (DNL) and adipose tissue fat composition are factors
that could determine liver fat composition. Since the end product of DNL are
saturated fatty acids and as the majority of fatty acids in the liver originate
from adipose tissue, both may influence hepatic fatty acid composition
profoundly. Up to now, relations between hepatic fatty acid composition, DNL
and adipose tissue fatty acid composition have never been determined in the
same study.
Study objective
The primary objective of this study is to determine the association between DNL
and hepatic %SFA in overweight/obese subjects differing in liver fat content.
The secondary objectives are to determine the association between adipose
tissue fat composition and liver fat composition and the association between
liver fat composition and liver, muscle and whole body insulin sensitivity.
Study design
This is a cross-sectional observational study.
Twenty-two volunteers, 8 with liver fat content <5% and 14 with liver content
>5%, will take part in the total study. MRS measurements will be performed on
approximately 31 subjects to determine amongst others liver fat content, based
on liver fat content it will be determined whether subjects can take part in
the rest of the study.
In this study liver fat content and composition (MRS), adipose tissue
composition (MRS and biopsy), de novo lipogenesis (D2O in VLDL-TG), liver,
muscle and whole body insulin sensitivity (2 step hyperinsulinemic euglycemic
clamp and biopsy) and body composition (BodPod) will be measured.
Study burden and risks
Results of this study will provide insight in the relation between factors that
influence liver fat and liver fat composition and in the clinical relevance of
liver fat composition in humans. The risks of the performed measurements and
the physical discomfort are low; risks related to the clamp, adipose tissue
biopsy, muscle biopsy, DNL measurement and MRS measurements are low because of
clear exclusion criteria aimed at reducing risks and the well-experienced
researchers performing these tests and isotopically-labelled water ingestion is
entirely safe and non-toxic with body water enrichment up to 20 mol%.
Universiteitssingel 50
Maastricht 6229 ER
NL
Universiteitssingel 50
Maastricht 6229 ER
NL
Listed location countries
Age
Inclusion criteria
Signed informed consent
Caucasian (people will be excluded when having a 50% or more then 50% racial African/Asian background)
Male or postmenopausal female
Aged 45-70 years at start of the study
Body mass index (BMI) 27 * 35 kg/m2
Stable dietary habits (no weight loss or gain >3kg in the past 3 months)
Sedentary lifestyle (not more than 2 hours of sports per week)
Exclusion criteria
Type 2 diabetes
Active diseases (cardiovascular, diabetes, liver, kidney, cancer or other)
Contra-indication for MRI
Alcohol consumption of >2 servings per day
Smoking >5 cigarettes per day
Use of anti-coagulants
Design
Recruitment
Followed up by the following (possibly more current) registration
No registrations found.
Other (possibly less up-to-date) registrations in this register
No registrations found.
In other registers
| Register | ID |
|---|---|
| CCMO | NL60263.068.16 |