Cellular sensors of feast and famine.
نویسنده
چکیده
In response to changes in environmental conditions, animals and humans alike can initiate physiological regulatory mechanisms to assure survival. For example, when food is scarce, the body becomes “thrifty”, and conversely, when it is abundant, physiological “unthrifty” mechanisms are initiated. Recent work has uncovered novel cellular mechanisms of fuel sensing that contribute to these shifts and has established a potential relationship between these responses and the common metabolic phenotype of insulin resistance. The first such mechanism to be identified depends on malonyl Co-A, which allosterically inhibits carnitine palmitoyl transferase (CPT1). Because this enzyme controls mitochondrial uptake, and hence oxidation, of longchain fatty acyl-CoAs (see Ruderman for review, ref. 1), malonyl-CoA can act as a fuel sensor to regulate the rate of fatty acid oxidation in muscle (Figure 1). Ten years ago, Marshall et al. (2) suggested that another fuel-sensing mechanism, this one dependent on the hexosamine biosynthesis pathway (blue arrows in Figure 1), mediates the cellular response to excess environmental glucose. These authors proposed that metabolism of glucose by this route, which typically represents 1-3% of total glucose metabolism, generates a cellular satiety signal that leads to decreased glucose uptake by insulin-sensitive cells. In this issue of the JCI, Obici et al. (3) propose that the hexosamine pathway is not only involved in glucose metabolism and insulin resistance, but may also be one of the biochemical links between nutrient availability and cellular energy metabolism. The activation or inhibition of this fuel sensing pathway may, therefore, play an important role in the regulation of energy balance. However, their present data raise significant questions about the role of transcriptional regulation in the adaptive response to energy surfeit.
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ورودعنوان ژورنال:
- The Journal of clinical investigation
دوره 109 12 شماره
صفحات -
تاریخ انتشار 2002