| Autor: |
Perreault, Mylene, Panza, Darrell, Will, Sarah, Harding, Kimberly, Jalenak, Mary, Bollag, Gideon, Ibrahim, Prabha, Artis, Rick, Lin, Jack, Saiah, Eddine, Mansour, Tarek, Tobin, James, Erbe, David |
| Předmět: |
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| Zdroj: |
Diabetes; Jun2007 Supplement 1, Vol. 56, pA338-A338, 1/5p |
| Abstrakt: |
Peraxisome proliferators activated receptors (PPARα, γ, and δ) serve as master regulators of glucose and lipid metabolism and were recently shown to play a role in nutrient sensing. While PPAR γ agonism commonly results in weight gain in animals and humans, PPAR α and δ agonism has demonstrated the potential to significantly induce fat burning and weight loss in animals. Here, we use a pan agonist that couples potent PPAR δ and α agonism with partial PPAR γ activity to determine the mechanism by which PPAR activation induces body weight loss in mice. Treatment of ob/ob and Diet-Induced Obese (DIO) mice with the pan agonist for 11-14 days significantly decreased body weights (19% decrease in ob/ob, p<0.05; 31% decrease in DIO, p<0.05). This weight loss was associated with a concomitant decrease in fat mass (54%, p<0.05), with no effect on lean mass despite animals losing nearly a third of their weight. One mechanism for the weight loss appears to be through induction of satiety with an approximately 50% reduction in food intake (p<0.05) seen in treated animals. Treated mice are also burning more fat as demonstrated by a respiratory exchange ratio near 0.7 for much of the day, while the overall metabolic rate is unchanged. In addition to inducing weight loss, the pan agonist lowered glucose, insulin and triglyceride levels by 65%, 85% and 90%, respectively. Pair-feeding studies revealed that these improvements in glucose and insulin levels were mostly independent of the reduction in food intake, while the triglyceride lowering and weight loss was more dependent on food consumption. On-going studies explore the contribution to satiety induction of peripheral PPAR signals (to the brain from vagal nerves) as well as induced fat burning. These findings provide insight into a mechanism for inducing metabolic efficacy coupled to weight loss with a pan PPAR agonist that could provide new avenues to treat metabolic diseases, including diabetes, dyslipidemia, and obesity. [ABSTRACT FROM AUTHOR] |
| Databáze: |
Complementary Index |
| Externí odkaz: |
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