Regulation of food intake by modulation of long-chain fatty acyl-CoA levels in the hypothalamus

• US 7,705,016 B2
• Filed: 02/12/2004
• Issued: 04/27/2010
• Est. Priority Date: 02/13/2003
• Status: Expired due to Fees

• Current Assignee: National Institutes of Health (NIH) (Government of the United States of America)
• Original Assignee: Albert Einstein College of Medicine of Yeshiva University
• Inventors: Obici, Silvana, Rossetti, Luciano
• Primary Examiner(s): Weddington; Kevin
• Application Number:
  US10/545,056
• Publication Number:
  US 20070093434A1
• Time in Patent Office: 2,266 Days
• Field of Search: 514/305, 514/357, 514/381, 514/476, 514/588, 514/560, 514/909, 514/866
• US Class Current: 514/305
• CPC Class Codes: A61K 2039/505 comprising antibodies
• CPC Class Codes: A61K 38/00 Medicinal preparations containing peptides peptides containing beta-lactam rings A61K31/00; cyclic dipeptides not having in their molecule any other peptide link than those which form their ring, e.g. piperazine-2,5-diones, A61K31/00; ergot alkaloids of the cyclic peptide type A61K31/48; containing macromolecular compounds having statistically distributed amino acid units A61K31/74; medicinal preparations containing antigens or antibodies A61K39/00; medicinal preparations characterised by the non-active ingredients, e.g. peptides as drug carriers, A61K47/00
• CPC Class Codes: A61K 48/00 Medicinal preparations containing genetic material which is inserted into cells of the living body to treat genetic diseases; Gene therapy
• CPC Class Codes: A61K 48/0075 characterised by an aspect of the delivery route, e.g. oral, subcutaneous
• CPC Class Codes: A61P 1/16 for liver or gallbladder disorders, e.g. hepatoprotective agents, cholagogues, litholytics
• CPC Class Codes: A61P 15/08 for gonadal disorders or for enhancing fertility, e.g. inducers of ovulation or of spermatogenesis
• CPC Class Codes: A61P 3/04 Anorexiants; Antiobesity agents
• CPC Class Codes: A61P 3/08 for glucose homeostasis pancreatic hormones A61P5/48
• CPC Class Codes: A61P 3/10 for hyperglycaemia, e.g. antidiabetics
• CPC Class Codes: A61P 31/12 Antivirals
• CPC Class Codes: A61P 31/18 for HIV
• CPC Class Codes: A61P 35/00 Antineoplastic agents
• CPC Class Codes: C07K 16/18 against material from animals or humans
• CPC Class Codes: C07K 16/28 against receptors, cell surface antigens or cell surface determinants
• CPC Class Codes: C12N 15/1137 against enzymes viral enzymes C12N15/1131; receptors C12N15/1138
• CPC Class Codes: C12N 2310/11 Antisense
• CPC Class Codes: C12N 2310/12 catalytic nucleic acids, e.g. ribozymes
• CPC Class Codes: C12N 2310/14 interfering N.A.
• CPC Class Codes: C12N 2799/04 in vivo
• CPC Class Codes: C12N 9/1029 transferring groups other than amino-acyl groups (2.3.1)
• CPC Class Codes: C12Y 203/01021 : Carnitine O-palmitoyltransferase (2.3.1.21)

Abstract

Methods of reducing food intake and glucose production in a mammal, or restoring hepatic autoregulation are provided. The methods involve increasing long-chain fatty acyl-Co-A (LC-CoA) levels in the hypothalamus, or stimulating efferent fibers in the hepatic branch of the vagus nerve. Also provided are methods of increasing food intake and glucose production in a mammal. The methods involve decreasing long-chain fatty acyl-Co-A (LC-CoA) levels in the hypothalamus of the mammal.

Claims

1. A method of reducing food intake in a mammal, the method comprising administering to the mammal a pharmaceutical composition comprising a small molecule capable of inhibiting carnitine palmitoyl transferase 1 (CPT1) in the brain of a mammal, wherein the pharmaceutical composition is administered in an amount and manner effective to reduce food intake in the mammal, wherein the pharmaceutical composition is administered to the brain such that the small molecule enters the hypothalamus or the pharmaceutical composition is administered such that the small molecule crosses the blood brain barrier, and wherein the small molecule capable of inhibiting CPT1 is 2-tetradecylglydate (TDGA) or (R)-N-(tetradecylcarbamoyl)-aminocarnitine.

2. The method of claim 1, wherein the small molecule capable of inhibiting CPT1 is 2-tetradecylglydate (TDGA).

3. The method of claim 1, wherein the small molecule capable of inhibiting CPT1 is (R)-N-(tetradecylcarbamoyl)-aminocarnitine.