Chronic Intranasal Insulin Does Not Affect Hepatic Lipids but Lowers Circulating BCAAs in Healthy Male Subjects.
BACKGROUND
Nonalcoholic fatty liver disease and elevated circulating branched-chain amino acids (BCAAs) are common characteristics of obesity and type 2 diabetes. In rodents, brain insulin signaling controls both hepatic triglyceride secretion and BCAA catabolism. Whether brain insulin signaling controls similar metabolic pathways in humans is unknown.


OBJECTIVE
Here we assessed if intranasal insulin, a method to preferentially deliver insulin to the central nervous system, is able to modulate hepatic lipid content and plasma BCAAs in humans.


METHODS
We conducted a randomized, double-blind, placebo-controlled trial at the Medical University of Vienna.


METHODS
We assessed if a chronic 4-week intranasal insulin treatment (40 IU, 4 times daily) reduces hepatic triglyceride content and circulating BCAAs in 20 healthy male volunteers.


METHODS
Hepatic lipid content was assessed noninvasively by 1H-magnetic resonance spectroscopy, and BCAAs were measured by gas chromatography mass spectrometry at defined time points during the study.


RESULTS
Chronic intranasal insulin treatment did not alter body weight, body mass index, and hepatic lipid content but reduced circulating BCAA levels.


CONCLUSIONS
These findings support the notion that brain insulin controls BCAA metabolism in humans. Thus, brain insulin resistance could account at least in part for the elevated BCAA levels observed in the insulin-resistant state.
Department of Medicine III, Division of Endocrinology and Metabolism.
Thomas
T
Scherer
Department of Medicine III, Division of Endocrinology and Metabolism.
Peter
P
Wolf
Department of Medicine III, Division of Endocrinology and Metabolism.
Sabina
S
Smajis
National Research Council Institute of Clinical Physiology, 56124 Pisa, Italy.
Melania
M
Gaggini
Department of Medicine III, Division of Endocrinology and Metabolism.
Martina
M
Hackl
National Research Council Institute of Clinical Physiology, 56124 Pisa, Italy.
Amalia
A
Gastaldelli
Section for Science of Complex Systems, CeMSIIS.
Peter
P
Klimek
Department of Laboratory Medicine, and.
Elisa
E
Einwallner
Department of Laboratory Medicine, and.
Rodrig
R
Marculescu
Department of Medicine III, Division of Endocrinology and Metabolism.
Anton
A
Luger
Department of Medicine III, Division of Endocrinology and Metabolism.
Clemens
C
Fürnsinn
High Field MR Centre, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.
Siegfried
S
Trattnig
Department of Medicine and Department of Neuroscience, Diabetes, Obesity and Metabolism Institute, Icahn School of Medicine at Mount Sinai, New York, New York 10029.
Christoph
C
Buettner
Department of Medicine III, Division of Endocrinology and Metabolism.|High Field MR Centre, Department of Biomedical Imaging and Image Guided Therapy, Medical University of Vienna, 1090 Vienna, Austria.
Martin
M
Krššák
Department of Medicine III, Division of Endocrinology and Metabolism.
Michael
M
Krebs
D000281:Administration, Intranasal; D000328:Adult; D000597:Amino Acids, Branched-Chain / Q000097:blood*; D004311:Double-Blind Method; D015536:Down-Regulation; D004334:Drug Administration Schedule; D064368:Healthy Volunteers; D006801:Humans; D007328:Insulin / Q000008:administration & dosage* / Q000009:adverse effects; D050356:Lipid Metabolism / Q000187:drug effects*; D008055:Lipids / Q000032:analysis; D008099:Liver / Q000737:chemistry / Q000187:drug effects* / Q000378:metabolism*; D008297:Male; D010919:Placebos
D000597:Amino Acids, Branched-Chain; D007328:Insulin; D008055:Lipids; D010919:Placebos