Effects of dietary n-3 fatty acids on hepatic and peripheral insulin sensitivity in insulin-resistant humans

Antigoni Z. Lalia, Matthew L. Johnson, Michael Dennis Jensen, Kazanna C. Hames, John D Port, Ian R Lanza

Research output: Contribution to journalArticle

23 Citations (Scopus)

Abstract

OBJECTIVE: Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-standard measurements. RESEARCH DESIGN AND METHODS: Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6 months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with somatostatin was used to assess hepatic and peripheral insulin sensitivity. Postprandial glucose disposal and insulin secretion were measured after a meal. Measurements were performed at baseline and after 6 months of treatment. Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was measured in isolated mitochondria using high-resolution respirometry and noninvasively by magnetic resonance spectroscopy. RESULTS: Compared with placebo, EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the suppression of endogenous glucose production by insulin, exhibited a small but significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial function was unchanged by EPA+DHA or placebo. CONCLUSIONS: This study demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal, insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity with EPA+DHA, but this was not associated with any improvements in clinically meaningful outcomes.

Original languageEnglish (US)
Pages (from-to)1228-1237
Number of pages10
JournalDiabetes Care
Volume38
Issue number7
DOIs
StatePublished - Jul 1 2015

Fingerprint

Eicosapentaenoic Acid
Docosahexaenoic Acids
Omega-3 Fatty Acids
Insulin Resistance
Insulin
Liver
Placebos
Glucose
Muscles
Abdominal Fat
Glucose Clamp Technique
Organelle Biogenesis
Somatostatin
Double-Blind Method
Gold
Meals
Rodentia
Mitochondria
Skeletal Muscle
Research Design

ASJC Scopus subject areas

  • Internal Medicine
  • Endocrinology, Diabetes and Metabolism
  • Advanced and Specialized Nursing

Cite this

Effects of dietary n-3 fatty acids on hepatic and peripheral insulin sensitivity in insulin-resistant humans. / Lalia, Antigoni Z.; Johnson, Matthew L.; Jensen, Michael Dennis; Hames, Kazanna C.; Port, John D; Lanza, Ian R.

In: Diabetes Care, Vol. 38, No. 7, 01.07.2015, p. 1228-1237.

Research output: Contribution to journalArticle

@article{3b788a5708bb4d7baf793de64e54a8eb,
title = "Effects of dietary n-3 fatty acids on hepatic and peripheral insulin sensitivity in insulin-resistant humans",
abstract = "OBJECTIVE: Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-standard measurements. RESEARCH DESIGN AND METHODS: Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6 months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with somatostatin was used to assess hepatic and peripheral insulin sensitivity. Postprandial glucose disposal and insulin secretion were measured after a meal. Measurements were performed at baseline and after 6 months of treatment. Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was measured in isolated mitochondria using high-resolution respirometry and noninvasively by magnetic resonance spectroscopy. RESULTS: Compared with placebo, EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the suppression of endogenous glucose production by insulin, exhibited a small but significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial function was unchanged by EPA+DHA or placebo. CONCLUSIONS: This study demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal, insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity with EPA+DHA, but this was not associated with any improvements in clinically meaningful outcomes.",
author = "Lalia, {Antigoni Z.} and Johnson, {Matthew L.} and Jensen, {Michael Dennis} and Hames, {Kazanna C.} and Port, {John D} and Lanza, {Ian R}",
year = "2015",
month = "7",
day = "1",
doi = "10.2337/dc14-3101",
language = "English (US)",
volume = "38",
pages = "1228--1237",
journal = "Diabetes Care",
issn = "1935-5548",
publisher = "American Diabetes Association Inc.",
number = "7",

}

TY - JOUR

T1 - Effects of dietary n-3 fatty acids on hepatic and peripheral insulin sensitivity in insulin-resistant humans

AU - Lalia, Antigoni Z.

AU - Johnson, Matthew L.

AU - Jensen, Michael Dennis

AU - Hames, Kazanna C.

AU - Port, John D

AU - Lanza, Ian R

PY - 2015/7/1

Y1 - 2015/7/1

N2 - OBJECTIVE: Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-standard measurements. RESEARCH DESIGN AND METHODS: Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6 months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with somatostatin was used to assess hepatic and peripheral insulin sensitivity. Postprandial glucose disposal and insulin secretion were measured after a meal. Measurements were performed at baseline and after 6 months of treatment. Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was measured in isolated mitochondria using high-resolution respirometry and noninvasively by magnetic resonance spectroscopy. RESULTS: Compared with placebo, EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the suppression of endogenous glucose production by insulin, exhibited a small but significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial function was unchanged by EPA+DHA or placebo. CONCLUSIONS: This study demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal, insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity with EPA+DHA, but this was not associated with any improvements in clinically meaningful outcomes.

AB - OBJECTIVE: Dietary n-3 polyunsaturated fatty acids, including eicosapentaenoic acid (EPA) and docosahexaenoic acid (DHA), prevent insulin resistance and stimulate mitochondrial biogenesis in rodents, but the findings of translational studies in humans are thus far ambiguous. The aim of this study was to evaluate the influence of EPA and DHA on insulin sensitivity, insulin secretion, and muscle mitochondrial function in insulin-resistant, nondiabetic humans using a robust study design and gold-standard measurements. RESEARCH DESIGN AND METHODS: Thirty-one insulin-resistant adults received 3.9 g/day EPA+DHA or placebo for 6 months in a randomized double-blind study. Hyperinsulinemic-euglycemic clamp with somatostatin was used to assess hepatic and peripheral insulin sensitivity. Postprandial glucose disposal and insulin secretion were measured after a meal. Measurements were performed at baseline and after 6 months of treatment. Abdominal fat distribution was evaluated by MRI. Muscle oxidative capacity was measured in isolated mitochondria using high-resolution respirometry and noninvasively by magnetic resonance spectroscopy. RESULTS: Compared with placebo, EPA+DHA did not alter peripheral insulin sensitivity, postprandial glucose disposal, or insulin secretion. Hepatic insulin sensitivity, determined from the suppression of endogenous glucose production by insulin, exhibited a small but significant improvement with EPA+DHA compared with placebo. Muscle mitochondrial function was unchanged by EPA+DHA or placebo. CONCLUSIONS: This study demonstrates that dietary EPA+DHA does not improve peripheral glucose disposal, insulin secretion, or skeletal muscle mitochondrial function in insulin-resistant nondiabetic humans. There was a modest improvement in hepatic insulin sensitivity with EPA+DHA, but this was not associated with any improvements in clinically meaningful outcomes.

UR - http://www.scopus.com/inward/record.url?scp=84958597386&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=84958597386&partnerID=8YFLogxK

U2 - 10.2337/dc14-3101

DO - 10.2337/dc14-3101

M3 - Article

C2 - 25852206

AN - SCOPUS:84958597386

VL - 38

SP - 1228

EP - 1237

JO - Diabetes Care

JF - Diabetes Care

SN - 1935-5548

IS - 7

ER -