title: Metabolic Effects of Long-Term Reduction in Free Fatty Acids With Acipimox in Obesity: A Randomized Trial.
abstract: BACKGROUND
  Increased circulating free fatty acids (FFAs) have been proposed to contribute to insulin resistance in obesity. Short-term studies have investigated the effects of acipimox, an inhibitor of hormone-sensitive lipase, on glucose homeostasis, but longer-term studies have not been performed.
  
  
  OBJECTIVE
  To test the hypothesis that long-term treatment with acipimox would reduce FFA and improve insulin sensitivity among nondiabetic, insulin-resistant, obese subjects.
  
  
  METHODS
  At an academic medical center, 39 obese men and women were randomized to acipimox 250 mg thrice-daily vs identical placebo for 6 months.
  
  
  METHODS
  Plasma lipids, insulin sensitivity, adiponectin, and mitochondrial function via assessment of the rate of post-exercise phosphocreatine recovery on (31)P-magnetic resonance spectroscopy as well as muscle mitochondrial density and relevant muscle gene expression.
  
  
  RESULTS
  Fasting glucose decreased significantly in acipimox-treated individuals (effect size, -6 mg/dL; P = .02), in parallel with trends for reduced fasting insulin (effect size, -6.8 μU/mL; P = .07) and HOMA-IR (effect size, -1.96; P = .06), and significantly increased adiponectin (effect size, +668 ng/mL; P = .02). Acipimox did not affect insulin-stimulated glucose uptake, as assessed by euglycemic, hyperinsulinemic clamp. Effects on muscle mitochondrial function and density and on relevant gene expression were not seen.
  
  
  CONCLUSIONS
  These data shed light on the long-term effects of FFA reduction on insulin sensitivity, other metabolic parameters, and muscle mitochondrial function in obesity. Reduced FFA achieved by acipimox improved fasting measures of glucose homeostasis, lipids, and adiponectin but had no effect on mitochondrial function, mitochondrial density, or muscle insulin sensitivity.
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Hideo
authors.initials: H
authors.lastname: Makimura
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Takara L
authors.initials: TL
authors.lastname: Stanley
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Caroline
authors.initials: C
authors.lastname: Suresh
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Ana Luisa
authors.initials: AL
authors.lastname: De Sousa-Coelho
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Walter R
authors.initials: WR
authors.lastname: Frontera
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Stephanie
authors.initials: S
authors.lastname: Syu
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Laurie R
authors.initials: LR
authors.lastname: Braun
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Sara E
authors.initials: SE
authors.lastname: Looby
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Meghan N
authors.initials: MN
authors.lastname: Feldpausch
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Martin
authors.initials: M
authors.lastname: Torriani
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Hang
authors.initials: H
authors.lastname: Lee
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Mary-Elizabeth
authors.initials: ME
authors.lastname: Patti
authors.affiliation: Program in Nutritional Metabolism and Neuroendocrine Unit (H.M., T.L.S., C.S., S.S., L.R.B., S.E.L., M.N.F., S.K.G.), Massachusetts General Hospital, Boston, Massachusetts 02114; Harvard Medical School (H.M., T.L.S., A.L.D.S.-C., L.R.B., S.E.L., M.T., H.L., M.-E.P., S.K.G.), Boston, Massachusetts 02115; Pediatric Endocrine Unit (T.L.S., L.R.B.), Massachusetts General Hospital, Boston, Massachusetts 02114; Research Division (A.L.D.S.-C., M.-E.P.), Joslin Diabetes Center, Boston, Massachusetts 02215; Department of Physical Medicine and Rehabilitation (W.R.F.), Vanderbilt University Medical Center, Nashville, Tennessee 37212; Department of Physical Medicine and Rehabilitation (W.R.F.), Harvard Medical School/Spaulding Rehabilitation Hospital, Boston, Massachusetts 02114; Department of Physiology (W.R.F.), University of Puerto Rico School of Medicine, San Juan, Puerto Rico 00936; Department of Radiology (M.T.), Massachusetts General Hospital, Boston, Massachusetts 02114; and MGH Biostatistics Center (H.L.), Massachusetts General Hospital and Harvard Medical Center, Boston, Massachusetts 02114.
authors.forename: Steven K
authors.initials: SK
authors.lastname: Grinspoon
mesh_terms: D000328:Adult; D001786:Blood Glucose / Q000378:metabolism; D001823:Body Composition / Q000187:drug effects; D015536:Down-Regulation / Q000187:drug effects; D004734:Energy Metabolism / Q000187:drug effects; D005230:Fatty Acids, Nonesterified / Q000097:blood*; D005260:Female; D006801:Humans; D000960:Hypolipidemic Agents / Q000627:therapeutic use*; D050356:Lipid Metabolism / Q000187:drug effects; D008297:Male; D008875:Middle Aged; D009765:Obesity / Q000097:blood* / Q000188:drug therapy* / Q000378:metabolism; D011719:Pyrazines / Q000627:therapeutic use*; D055815:Young Adult
chemical_list: D001786:Blood Glucose; D005230:Fatty Acids, Nonesterified; D000960:Hypolipidemic Agents; D011719:Pyrazines; C027696:acipimox