Long-term correction of obesity and diabetes in genetically obese mice by a single intramuscular injection of recombinant adeno-associated virus encoding mouse leptin

The ob/ob mouse is genetically deficient in leptin and exhibits a phenotype that includes obesity and non-insulin-dependent diabetes melitus. This phenotype closely resembles the morbid obesity seen in humans. In this study, we demonstrate that a single intramuscular injection of a recombinant adeno-associated virus (AAV) vector encoding mouse leptin (rAAV-leptin) in ob/ob mice leads to prevention of obesity and diabetes. The treated animals show normalization of metabolic abnormalities including hyperglycemia, insulin resistance, impaired glucose tolerance, and lethargy. The effects of a single injection have lasted through the 6-month course of the study. At all time points measured the circulating levels of leptin in the serum were similar to age-matched control C57 mice. These results demonstrate that maintenance of normal levels of leptin (2–5 ng/ml) in the circulation can prevent both the onset of obesity and associated non-insulin-dependent diabetes. Thus a single injection of a rAAV vector expressing a therapeutic gene can lead to complete and long-term correction of a genetic disorder. Our study demonstrates the long-term correction of a disease caused by a genetic defect and proves the feasibility of using rAAV-based vectors for the treatment of chronic disorders like obesity.

Employment and income distribution objectives for A.I.D. programs and policies /

Includes bibliographical references.

Greek papyri in the library of Cornell University,/

Autographed from type-written copy.

Highway collision investigation training program. Final report.

National Highway Traffic Safety Administration, Washington, D.C.

Police traffic services basic training program course guide. Volume 1 of 3.

National Highway Traffic Safety Administration, Washington, D.C.

Item analysis /

Thesis (M. S.)--University of Illinois at Urbana-Champaign.

A graph-structure transformation model for picture parsing,

"COO-2118-0031."

Parallel image-processing for automated cervical smear analysis,

"COO-2118-0029."

The rhythm way to family happiness; a lifetime reference for the use of the rhythm method,

Mode of access: Internet.

Seismic source functions for closely-spaced simultaneous nuclear detonations /

"February 1973."

The Sabbath recorder.

Published in: Alfred Center, N.Y., June 27, 1872-1894; in: Plainfield, N.J., 1895-<1972>; in: Janesville, Wis, May 1982-

The life and correspondence of the Sir Bartle Frere, bart., G.C.B., F.R.S., etc.

Mode of access: Internet.

Dependent and neglected children : report of the Committee on Socially Handicapped--Dependency and Neglect /

"Section IV--The handicapped: prevention, maintenance, protection. C. C. Carsten, Chairman."--p. [iii]

The De La Rue history of British & foreign postage stamps, 1855 to 1901 /

Includes index.