There is growing evidence that the postnatal environment can have a major impact on the development of obesity and insulin resistance in offspring. We postulated that cross-fostering obesity-prone offspring to lean, obesity-resistant dams would ameliorate their development of obesity and insulin resistance, while fostering lean offspring to genetically obese dams would lead them to develop obesity and insulin resistance as adults. We found that obesity-prone pups cross-fostered to obesity-resistant dams remained obese but did improve their insulin sensitivity as adults. In contrast, obesity-resistant pups cross-fostered to genetically obese dams showed a diet-induced increase in adiposity, reduced insulin sensitivity, and associated changes in hypothalamic neuropeptide, insulin, and leptin receptors, which might have contributed to their metabolic defects. There was a selective increase in insulin levels and differences in fatty acid composition of obese dam milk which might have contributed to the increased adiposity, insulin resistance, and hypothalamic changes in obesity-resistant cross-fostered offspring. These results demonstrate that postnatal factors can overcome both genetic predisposition and prenatal factors in determining the development of adiposity, insulin sensitivity, and the brain pathways that mediate these functions. diet-induced obesity; hypothalamus; milk; development; plasticity; Agouti-related peptide; leptin MATERNAL INTAKE of a high-fat diet and the presence of obesity during pregnancy and lactation promote obesity in offspring, particularly in individuals with an obesity-prone genetic background (21,32,36,55). However, there is growing evidence that a variety of manipulations during the postnatal environment can override prenatal factors and increase the risk of developing metabolic disorders such as obesity and diabetes later in life. Raising pups in small litters leads to increased milk intake and the development of obesity, whereas raising pups in large litters has the opposite effect (16,23,26). Administration of insulin during early postnatal development results in obesity and altered development of hypothalamic neuropeptide systems involved in energy homeostasis (22, 50). Cross-fostering pups is another method of assessing the role of the postnatal environment in later development. A single study in mice has demonstrated that fostering inbred obesity-prone mouse pups with obesity-resistant dams attenuates their obesity, whereas fostering obesity-resistant pups with obesity-prone dams causes them to develop obesity and insulin resistance (51).Unlike many rodent models, the majority of human obesity is inherited as a polygenic disorder (6). For that reason, we have used a rat model of diet-induced obesity (DIO), in which obesity is also inherited as a polygenic trait (33, 38) in association with insulin resistance (33), hypertension (14), and hyperlipidemia (62). These rats also have several abnormalities of brain function, which antedate and may contribute to the later development o...

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The contribution of a-and t-amino nitrogen atoms to pyrazine formation in the reaction of labeled lysine with glucose was investigated. The labeled lysine, which contained a 15N isotope labeled at the a-amino group and a 14N at the t-amino group, was reacted with glucose a t different pHs and temperatures in a dry system. A similar reaction mixture was also studied in an aqueous system a t 180 "C and pH 8.5. Pyrazine, methylpyrazine, ethylpyrazine, 2,6-dimethylpyrazine, 2,3-dimethylpyrazine, vinylpyrazine, 2-ethyl-5-methylpyrazine, 2-ethyl-6-methylpyrazine, 2-vinyl-5-methylpyrazine, and trimethylpyrazine were identified in the dry system. All pyrazines identified in the dry system were also found in the aqueous system. Two additional pyrazines, three pyridines, and one pyrrole were also observed in the aqueous system. Both the a-and t-amino groups of lysine were involved in pyrazine generation. The nitrogen atoms from a-amino groups of lysine react more readily with dicarbonyls to form pyrazines than the nitrogen atoms from t-amino groups. The amounts of pyrazines significantly decreased as the reaction temperature decreased. Neither the reaction temperature nor the pH of the reaction mixture had any effect on the contribution of the two different amino groups to pyrazine formation.

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Various components of garlic and aged garlic extract, including allicin, S-allylcysteine (SAC) and volatile metabolites of allicin were determined in breath, plasma and simulated gastric fluids by HPLC, gas chromatography (GC) or HPLC- and GC-mass spectrometry (MS). Data indicate that allicin decomposes in stomach acid to release allyl sulfides, disulfides and other volatiles that are postulated to be metabolized by glutathione and/or S-adenosylmethionine to form allyl methyl sulfide. SAC can be absorbed by the body and can be determined in plasma by HPLC or HPLC-MS using atmospheric pressure chemical ionization (APCI)-MS.