ObesityNCT01612234
Saturated Fat Versus Monounsaturated Fat and Insulin Action
A study testing High palmitate or high oleate diet. in people with Obesity, run by University of Vermont at 1 site in United States.
Trial summary
High intakes of saturated fat are associated with diabetes. Our work has shown that the two most common fatty acids in the North American diet, palmitic acid (saturated fat) and oleic acid (monounsaturated fat) are metabolized differently and have opposite effects on fat burning. Read more about this study
- Who is it for?
- Ages 18 to 40 yearsHealthy volunteers can take part
- Conditions the study is for
- Obesity
- What is being tested?
- High palmitate or high oleate diet.
- Could I receive a placebo?
- No, everyone receives an active treatment
- How many people
- 70 participants
- Where
- 1 siteUnited States
- Study dates
- Apr 2010to Nov 2015
- Phase
- Interventional
- Are there results?
- None posted in the registry
Key requirements
Who can take part, as listed by the sponsor. Only the study team can confirm whether you are eligible, so take this list to your doctor.
- Ages 18 to 40 years
- All sexes
- Healthy volunteers accepted
- Adult
Who may be able to join
- healthy young adults,
- 18 - 40 years of age
Who cannot join
- regular aerobic exercise training,
- dyslipidemia, and
- type 2 diabetes or insulin resistance
Trial locations and contacts
1 site in 1 country.
United States1 site
The Unversity of Vermont Clinical Research Center at Fletcher Allen Health Care
Burlington, Vermont, 05401
About this study
Official title: Palmitate Metabolism and Insulin Resistance
High intakes of saturated fat are associated with diabetes. Our work has shown that the two most common fatty acids in the North American diet, palmitic acid (saturated fat) and oleic acid (monounsaturated fat) are metabolized differently and have opposite effects on fat burning. The proposed study will examine biochemical and molecular mechanisms for how a high saturated fat diet versus a low saturated fat/high monounsaturated fat diet alters the action of the hormone, insulin, in skeletal muscle.
Read the detailed description
Palmitic acid (PA), impairs insulin sensitivity in skeletal muscle, and replacing PA in the diet with oleic acid (OA), a monounsaturated fatty acid (FA), may be beneficial. The first objective of this project is to understand the effects on lipid metabolism and skeletal muscle lipid composition, insulin signaling, and inflammatory signaling of two common variations in FA composition of the diet: (1) The typical intake of North America where PA and OA are present in equal proportions (HI PA diet). (2) The Mediterranean FA composition in which PA is much lower and OA much higher (HI OA diet). PA may induce insulin resistance in skeletal muscle cells via its accumulation in lipids within muscle cells and via activation of inflammatory signaling. The second objective of this project is to assess the hypothesis that a high intake of PA will down-regulate its own one-carbon (initial) oxidation, leading to increased inflammatory signaling and decreased insulin signaling. However, there is literature evidence that FA may induce defects in insulin signaling, if FA are not completely oxidized; therefore, the third objective is to assess the hypotheses that a high PA diet may decrease complete oxidation of FA and possibly accelerate initial FA oxidation. A double-masked, cross-over trial of the effects of a high PA diet versus a high OA/low PA diet in 16 overweight or obese subjects and 16 lean subjects (aged 18 - 40 yr) will be conducted to investigate the following Specific Aims:
- To test the hypothesis that increased intake of PA will cause a decreased rate of [1-13C]-PA oxidation and will be associated with: (a) increased inflammatory signaling, within the muscle and by peripheral blood mononuclear cells; (b) Decreased insulin signaling as characterized by decreased, whole body, peripheral insulin sensitivity (euglycemic/hyperinsulinemic clamp) and, in skeletal muscle, decreased phospho-AKT (Ser473), increased phospho-IRS-1 (Ser636/Ser639), decreased tyrosine phosphorylation of IRS-1, and decreased membrane content of GLUT4.
- To test the hypothesis that increased intake of PA will cause less complete mitochondrial fatty acid oxidation, perhaps associated with dysfunction of the TCA cycle and increased reactive oxygen species formation. This hypothesis will be tested by measuring whole body and muscle (upper limb) relative rates of oxidation of [13-13C]-PA and [1-13C]-PA and by determining the serum profile of acylcarnitines, the urine concentrations of organic acids, and muscle concentrations of protein carbonyls.
- To test the hypothesis that a high PA diet will lead to less complete oxidation of FA, less insulin signaling in skeletal muscle in response to a test meal, less whole body insulin sensitivity, increased dysfunction of the TCA cycle, and greater reactive oxygen species formation compared to the results obtained in obese versus lean humans.
- Conditions
- Obesity
- Being tested
- High palmitate or high oleate diet.
- Keywords
- humans, lean, obese, saturated fat, monounsaturated fat, insulin sensitivity, inflammation, oxidant stress
- Medical subject headings
- Obesity, Insulin Resistance, Inflammation
What participants receive
What participants receive. In a randomised study each person is assigned to one group by chance.
High palmitate or high oleate diet.Dietary supplement
High palmitate diet composition: Fat, 40.4% kcal; palmitic acid, 16.0% kcal; oleic acid,16.2% kcal. High oleate diet composition: Fat, 40.1% kcal; palmitic acid, 2.4% kcal; oleic acid, 28.8% kcal
| Study group | Role | What they receive |
|---|---|---|
| High palmitate or high oleate diet. | Experimental | This is a solid food diet in which vegetable oils are used to create a dietary fat composition similar to the average American/Western diet in which palmitic and oleic acid are ingested in approximately equal amounts (high palmitate diet) or a composition similar to the Mediterranean Diet (low palmitate, high oleate, using hazelnut oil as the source of fat). There are no interventions other than the diet itself. Receives: Dietary Supplement: High palmitate or high oleate diet. |
| high palmitate or high oleate diet | Experimental | This is a solid food diet in which vegetable oils are used to create a dietary fat composition similar to the average American/Western diet in which palmitic and oleic acid are ingested in approximately equal amounts (high palmitate diet) or a composition similar to the Mediterranean Diet (low palmitate, high oleate, using hazelnut oil as the source of fat). There are no interventions other than the diet itself. Receives: Dietary Supplement: High palmitate or high oleate diet. |
What is being measured
The primary outcome is the main question the study is designed to answer.
Whether increased palmitate balance (as measured by intake and the rate of [1-13C]-PA oxidation) causes increased insulin resistance and increased inflammatory signaling by peripheral blood mononuclear cells
Insulin sensitivity, inflammatory signaling, palmitate balance, and incomplete oxidation of palmitate in lean and obese young adults.
Measured: up to 4 yr
Secondary outcomes (1)
We will examine the link between palmitate intake and balance and oxidative stress measured using muscle and peripheral blood markers of oxidative stress and antioxidant responses.
activation of c-Jun N-terminal kinase (JNK) and heme oxygenase 1 in skeletal muscle in response to the diets.
Measured: up to 4 yr
Timeline
From the start of the study to its completion; the mark is today. Estimated dates are the sponsor’s plan.
- First posted5 Jun 2012 (estimated)
- Study startApr 2010
- Primary completionNov 2015
- Study completionNov 2015
Resources
- Official record on ClinicalTrials.govThe registry entry this page is built from, with its full change history.
- Publications (6)Papers the sponsor has linked to this study.
- Other trials for ObesityStudies of the same condition, open and under way.
- What the trial phases meanHow a treatment moves from first tests in people to approval.
More details
For doctors and researchers: how the study is designed, who runs it, and its registry IDs.
Study design
- Study type
- Interventional
- Phase
- Phase N/A
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind
- Who is masked
- Participant, Care provider, Investigator, Outcomes assessor
- Enrolment
- 70 participants (actual)
Sponsor and investigators
- Lead sponsor
- University of Vermont
- Sponsor type
- University, hospital or other
- Responsible party
- Principal investigator, Craig Lawrence Kien, University of Vermont
- Investigators
- Craig L. Kien, M.D, Ph.D., Principal investigator, The University of Vermont
IDs, dates and publications
- ClinicalTrials.gov ID
- NCT01612234
- Sponsor's protocol ID
- R01DK082803
- Status last verified
- Nov 2015
- First submitted
- 29 May 2012
- Last updated
- 2 Dec 2015
- Results posted
- No
- Data monitoring committee
- No
Publications
Kien CL, Everingham KI, D Stevens R, Fukagawa NK, Muoio DM. Short-term effects of dietary fatty acids on muscle lipid composition and serum acylcarnitine profile in human subjects. Obesity (Silver Spring). 2011 Feb;19(2):305-11. doi: 10.1038/oby.2010.135. Epub 2010 Jun 17.
PubMed 20559306Kien CL, Bunn JY, Stevens R, Bain J, Ikayeva O, Crain K, Koves TR, Muoio DM. Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans. Am J Clin Nutr. 2014 Mar;99(3):436-45. doi: 10.3945/ajcn.113.070557. Epub 2014 Jan 15.
PubMed 24429541Kien CL, Bunn JY, Tompkins CL, Dumas JA, Crain KI, Ebenstein DB, Koves TR, Muoio DM. Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood. Am J Clin Nutr. 2013 Apr;97(4):689-97. doi: 10.3945/ajcn.112.051730. Epub 2013 Feb 27.
PubMed 23446891Kien CL, Bunn JY, Poynter ME, Stevens R, Bain J, Ikayeva O, Fukagawa NK, Champagne CM, Crain KI, Koves TR, Muoio DM. A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults. Diabetes. 2013 Apr;62(4):1054-63. doi: 10.2337/db12-0363. Epub 2012 Dec 13.
PubMed 23238293Kien CL, Matthews DE, Poynter ME, Bunn JY, Fukagawa NK, Crain KI, Ebenstein DB, Tarleton EK, Stevens RD, Koves TR, Muoio DM. Increased palmitate intake: higher acylcarnitine concentrations without impaired progression of beta-oxidation. J Lipid Res. 2015 Sep;56(9):1795-807. doi: 10.1194/jlr.M060137. Epub 2015 Jul 8.
PubMed 26156077Kien CL, Bunn JY, Fukagawa NK, Anathy V, Matthews DE, Crain KI, Ebenstein DB, Tarleton EK, Pratley RE, Poynter ME. Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes. J Nutr Biochem. 2015 Dec;26(12):1599-606. doi: 10.1016/j.jnutbio.2015.07.014. Epub 2015 Aug 1.
PubMed 26324406
Study at a glance
From the registry record, last updated by the sponsor on 2 Dec 2015. Recruitment status is as the sponsor reported it: confirm with the study team.
- Official title
- Palmitate Metabolism and Insulin Resistance
- ClinicalTrials.gov ID
- NCT01612234
- Acronym / sponsor ID
- R01DK082803
- Conditions
- Obesity
- Keywords
- humans, lean, obese, saturated fat, monounsaturated fat, insulin sensitivity, inflammation, oxidant stress
- Study type
- Interventional
- Recruitment status
- Completed
- Enrolment
- 70 participants (actual)
- Lead sponsor
- University of VermontUniversity, hospital or other
- Study start
- Apr 2010
- Primary completion
- Nov 2015 (actual)
- Study completion
- Nov 2015 (actual)
- First posted
- 5 Jun 2012 (estimated)
- Results
- Not posted in the source record
Clinical summary
The research question as the sponsor registered it. This describes what the study plans to test, not what it found.
High intakes of saturated fat are associated with diabetes. Our work has shown that the two most common fatty acids in the North American diet, palmitic acid (saturated fat) and oleic acid (monounsaturated fat) are metabolized differently and have opposite effects on fat burning. The proposed study will examine biochemical and molecular mechanisms for how a high saturated fat diet versus a low saturated fat/high monounsaturated fat diet alters the action of the hormone, insulin, in skeletal muscle.
Detailed description
Palmitic acid (PA), impairs insulin sensitivity in skeletal muscle, and replacing PA in the diet with oleic acid (OA), a monounsaturated fatty acid (FA), may be beneficial. The first objective of this project is to understand the effects on lipid metabolism and skeletal muscle lipid composition, insulin signaling, and inflammatory signaling of two common variations in FA composition of the diet: (1) The typical intake of North America where PA and OA are present in equal proportions (HI PA diet). (2) The Mediterranean FA composition in which PA is much lower and OA much higher (HI OA diet). PA may induce insulin resistance in skeletal muscle cells via its accumulation in lipids within muscle cells and via activation of inflammatory signaling. The second objective of this project is to assess the hypothesis that a high intake of PA will down-regulate its own one-carbon (initial) oxidation, leading to increased inflammatory signaling and decreased insulin signaling. However, there is literature evidence that FA may induce defects in insulin signaling, if FA are not completely oxidized; therefore, the third objective is to assess the hypotheses that a high PA diet may decrease complete oxidation of FA and possibly accelerate initial FA oxidation. A double-masked, cross-over trial of the effects of a high PA diet versus a high OA/low PA diet in 16 overweight or obese subjects and 16 lean subjects (aged 18 - 40 yr) will be conducted to investigate the following Specific Aims:
- To test the hypothesis that increased intake of PA will cause a decreased rate of [1-13C]-PA oxidation and will be associated with: (a) increased inflammatory signaling, within the muscle and by peripheral blood mononuclear cells; (b) Decreased insulin signaling as characterized by decreased, whole body, peripheral insulin sensitivity (euglycemic/hyperinsulinemic clamp) and, in skeletal muscle, decreased phospho-AKT (Ser473), increased phospho-IRS-1 (Ser636/Ser639), decreased tyrosine phosphorylation of IRS-1, and decreased membrane content of GLUT4.
- To test the hypothesis that increased intake of PA will cause less complete mitochondrial fatty acid oxidation, perhaps associated with dysfunction of the TCA cycle and increased reactive oxygen species formation. This hypothesis will be tested by measuring whole body and muscle (upper limb) relative rates of oxidation of [13-13C]-PA and [1-13C]-PA and by determining the serum profile of acylcarnitines, the urine concentrations of organic acids, and muscle concentrations of protein carbonyls.
- To test the hypothesis that a high PA diet will lead to less complete oxidation of FA, less insulin signaling in skeletal muscle in response to a test meal, less whole body insulin sensitivity, increased dysfunction of the TCA cycle, and greater reactive oxygen species formation compared to the results obtained in obese versus lean humans.
Study design
- Primary purpose
- Prevention
- Allocation
- Randomised
- Intervention model
- Crossover
- Masking
- Quadruple blind (participant, care provider, investigator, outcomes assessor)
- Number of arms
- 2
| Arm | Type | Receives |
|---|---|---|
| High palmitate or high oleate diet. | Experimental | Dietary Supplement: High palmitate or high oleate diet.This is a solid food diet in which vegetable oils are used to create a dietary fat composition similar to the average American/Western diet in which palmitic and oleic acid are ingested in approximately equal amounts (high palmitate diet) or a composition similar to the Mediterranean Diet (low palmitate, high oleate, using hazelnut oil as the source of fat). There are no interventions other than the diet itself. |
| high palmitate or high oleate diet | Experimental | Dietary Supplement: High palmitate or high oleate diet.This is a solid food diet in which vegetable oils are used to create a dietary fat composition similar to the average American/Western diet in which palmitic and oleic acid are ingested in approximately equal amounts (high palmitate diet) or a composition similar to the Mediterranean Diet (low palmitate, high oleate, using hazelnut oil as the source of fat). There are no interventions other than the diet itself. |
Who may qualify
- Ages
- 18 to 40 years
- Sex
- All
- Healthy volunteers
- Accepted
- Age groups
- Adult
Key inclusion criteria (2 listed)
- healthy young adults,
- 18 - 40 years of age
Key exclusion criteria (3 listed)
- regular aerobic exercise training,
- dyslipidemia, and
- type 2 diabetes or insulin resistance
Eligibility is decided by the study team after screening; this overview does not establish that a patient qualifies. Full inclusion and exclusion criteria.
Interventions
| Intervention | Type | Arms |
|---|---|---|
| High palmitate or high oleate diet.High palmitate diet composition: Fat, 40.4% kcal; palmitic acid, 16.0% kcal; oleic acid,16.2% kcal. High oleate diet composition: Fat, 40.1% kcal; palmitic acid, 2.4% kcal; oleic acid, 28.8% kcal | Dietary supplement | High palmitate or high oleate diet., high palmitate or high oleate diet |
Primary outcome
Whether increased palmitate balance (as measured by intake and the rate of [1-13C]-PA oxidation) causes increased insulin resistance and increased inflammatory signaling by peripheral blood mononuclear cells
Time frame: up to 4 yr
Insulin sensitivity, inflammatory signaling, palmitate balance, and incomplete oxidation of palmitate in lean and obese young adults.
1 secondary outcome
We will examine the link between palmitate intake and balance and oxidative stress measured using muscle and peripheral blood markers of oxidative stress and antioxidant responses.
Time frame: up to 4 yr
Results and safety
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
Research links
- Official record on ClinicalTrials.govLast updated by the sponsor 2 Dec 2015.
- Background: PubMed 20559306Kien CL, Everingham KI, D Stevens R, Fukagawa NK, Muoio DM. Short-term effects of dietary fatty acids on muscle lipid composition and serum acylcarnitine profile in human subjects. Obesity (Silver Spring). 2011 Feb;19(2):305-11. doi: 10.1038/oby.2010.135. Epub 2010 Jun 17.
- Background: PubMed 24429541Kien CL, Bunn JY, Stevens R, Bain J, Ikayeva O, Crain K, Koves TR, Muoio DM. Dietary intake of palmitate and oleate has broad impact on systemic and tissue lipid profiles in humans. Am J Clin Nutr. 2014 Mar;99(3):436-45. doi: 10.3945/ajcn.113.070557. Epub 2014 Jan 15.
- Results publication: PubMed 23446891Kien CL, Bunn JY, Tompkins CL, Dumas JA, Crain KI, Ebenstein DB, Koves TR, Muoio DM. Substituting dietary monounsaturated fat for saturated fat is associated with increased daily physical activity and resting energy expenditure and with changes in mood. Am J Clin Nutr. 2013 Apr;97(4):689-97. doi: 10.3945/ajcn.112.051730. Epub 2013 Feb 27.
- Results publication: PubMed 23238293Kien CL, Bunn JY, Poynter ME, Stevens R, Bain J, Ikayeva O, Fukagawa NK, Champagne CM, Crain KI, Koves TR, Muoio DM. A lipidomics analysis of the relationship between dietary fatty acid composition and insulin sensitivity in young adults. Diabetes. 2013 Apr;62(4):1054-63. doi: 10.2337/db12-0363. Epub 2012 Dec 13.
- Results publication: PubMed 26156077Kien CL, Matthews DE, Poynter ME, Bunn JY, Fukagawa NK, Crain KI, Ebenstein DB, Tarleton EK, Stevens RD, Koves TR, Muoio DM. Increased palmitate intake: higher acylcarnitine concentrations without impaired progression of beta-oxidation. J Lipid Res. 2015 Sep;56(9):1795-807. doi: 10.1194/jlr.M060137. Epub 2015 Jul 8.
- Results publication: PubMed 26324406Kien CL, Bunn JY, Fukagawa NK, Anathy V, Matthews DE, Crain KI, Ebenstein DB, Tarleton EK, Pratley RE, Poynter ME. Lipidomic evidence that lowering the typical dietary palmitate to oleate ratio in humans decreases the leukocyte production of proinflammatory cytokines and muscle expression of redox-sensitive genes. J Nutr Biochem. 2015 Dec;26(12):1599-606. doi: 10.1016/j.jnutbio.2015.07.014. Epub 2015 Aug 1.
- Description of Kien Lab at the Division of Endocrinology, Diabetes, and Metabolism, Department of Medicine, The University of Vermont College of MedicineLink provided by the sponsor.
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Referral and contact
AzTrials does not enrol participants or take referrals. Contact the study team or a site listed below; they decide who can take part. This study is not recruiting at the moment.
Craig L. Kien, M.D, Ph.D. principal investigator
The University of Vermont
1 site in 1 country: see every site and its status.
Questions about this trial
What is this clinical trial studying?
A study testing High palmitate or high oleate diet. in people with Obesity, run by University of Vermont at 1 site in United States.
The full registered description is in the About this study section and the official record.
Who may be eligible to take part?
The sponsor lists 2 inclusion and 3 exclusion criteria. Eligibility is decided by the study team after screening, so read the full criteria and contact a listed site.
Is this clinical trial currently recruiting?
The record says: finished, as of the sponsor's last update on 2 Dec 2015. Status can change between updates, so confirm with the study contact before making plans.
Where is the study taking place?
The record lists 1 site in United States. Whether a site is taking part right now should be confirmed with that site. See every site.
What are the possible benefits and risks?
They depend on the study and the treatment, and no study can promise a benefit. The study team explains the known risks during informed consent, before anyone joins; the record itself does not list them.
Are results available for this study?
The study is completed, but results are not available in the source record. That does not mean the treatment did or did not work.
How can a doctor refer a patient or contact the research team?
The record lists no contact. The official record names the sponsor, who can be asked directly. AzTrials does not enrol participants or take referrals.
What does the primary outcome measure?
Whether increased palmitate balance (as measured by intake and the rate of [1-13C]-PA oxidation) causes increased insulin resistance and increased inflammatory signaling by peripheral blood mononuclear cells (time frame: up to 4 yr). It is what the study was designed to measure, not a finding.
Where can I read the original study information?
On the ClinicalTrials.gov record for NCT01612234, which also lists 6 linked publications.
Does a listing mean the treatment is approved or proven to work?
No. A listing means the study is registered. It does not show that the treatment is safe, works, or is approved by a regulator.
How often is this information updated?
AzTrials copies changed records from ClinicalTrials.gov every night and reloads the whole registry every week. The sponsor last updated this record on 2 Dec 2015.