Rodent Studies Look at Diet-Induced Obesity
Genetics can affect leptin sensitivity; active AKT1 gene mediates growth of type II muscle mass
TUESDAY, Feb. 12 (HealthDay News) -- Rat offspring of mothers that have a genetic predisposition to developing diet-induced obesity develop abnormal connections to the arcuate nucleus of the hypothalamus (ARH), a brain area that depends on leptin for normal development, according to research published in the February issue of Cell Metabolism.
Sebastien G. Bouret, Ph.D., of the University of Southern California in Los Angeles, and colleagues studied development of the ARH in brains of male rat pups born to rat dams bred to express the diet-induced obesity or diet-resistant genotypes. Diet-induced obese rats showed neurodevelopmental abnormalities in connections to the ARH, possibly as a result of decreased leptin sensitivity of these neurons. Bouret's team found these changes did not appear to be affected by the maternal diet, suggesting that leptin insensitivity in the ARH is inherited, resulting in obesity in response to diet.
In a second study published in the same journal, Yasuhiro Izumiya, M.D., Ph.D., of Boston University School of Medicine, and colleagues developed a transgenic diet-induced obese mouse in which the Akt1 transgene mediated growth of type II muscle mass. These mice showed reversible changes that led to reduced fat and body mass through increased muscle and whole-body metabolism, unrelated to physical activity or diet.
"The metabolic improvement in this model cannot be entirely explained by a reduction in fat-pad mass, indicating that type II muscle counteracts the actions of excess adipose tissue on whole-body metabolism," Izumiya and colleagues write. "These findings indicate that type II muscle has a previously unappreciated role in regulating whole-body metabolism through its ability to alter the metabolic properties of remote tissues."