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homeostasis may also be involved, including non-exercise activity thermogenesis (NEAT), which is the energy expended through minor involuntary muscle activity such as dgeting or maintaining posture ( 7). In addition, the ability to use particular metabolites could, in the long term, affect body fat mass. The hypothesis of nutrient balance suggests that for energy balance to be stable, the relative intake of a particular nutrient must match the proportion of that nutrient used in fuelling metabolism. Although this view of energy homeostasis may be over-simplistic, there is increasing evidence that a decrease in the ability to oxidize fatty acids may predispose some individuals towards weight gain ( 7).



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5.4.2.2 The asymptotic covarlance matrlx for maximum likelihood estimation from normally dlstributed observations An important characteristic of the maximum likelihood estimator of the parameters of nonlinear models is its asymptotic covariance matrix or, equivalently, the pertinent Cram&-Rao lower bound matrix. The Fisher information matrix for normally distributed observations is described by (4.40):

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in driving appetite for palatable food Brain Research, 952, 232 8. Langhans, W. and Geary, N. (2006) Regulation of body weight, in Obesity and Binge Eating Disorder (eds S. Munsch and C. Beglinger), Karger, Basel, pp. 21 40. Minokoshi, Y., Alquier, T., Furukawa, N., Kim, Y.B. et al. (2004) AMP-kinase regulates food intake by responding to hormonal and nutrient signals in the hypothalamus. Nature, 428, 569 74. Morley, J.E. (2007) Weight loss in older persons: new therapeutic approaches. Current Pharmaceutical Design, 13, 3637 47. Morton, G.J., Blevins, J.E., Williams, D.L. et al. (2005) Leptin action in the forebrain regulates the hindbrain response to satiety signals. The Journal of Clinical Investigation, 115, 703 10. Riedy, C.A., Chavez, M., Figlewicz, D.P. and Woods, S.C. (1995) Central insulin enhances sensitivity to cholecystokinin. Physiology & Behavior, 58, 755 60. Sandoval, D., Cota, D. and Seeley, R.J. (2008) The integrative role of CNS fuel-sensing mechanisms in energy balance and glucose regulation. Annual Review of Physiology, 70, 513 35. Schwartz, M.W. and Porte, D., Jr. (2005) Diabetes, obesity, and the brain. Science, 307, 375 9. Speakman, J.R. (2004) Obesity: the integrated roles of environment and genetics. The Journal of Nutrition, 134 (8 Suppl), 2090S 105S. Zafon, C. (2007) Oscillations in total body fat content through life: an evolutionary perspective. Obesity Reviews, 8, 525 30.

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load (Blaak et al., 2006; see Figure 7.8). Moreover, obese subjects adapt more slowly to a chronic high-fat diet as compared with lean individuals (Thomas et al., 1992). Additionally, post-obese women (i.e. who have lost weight, having previously been obese) (Astrup et al., 1994), or women predisposed to develop obesity (Raben, Macdonald and Astrup, 1994), have lower postprandial and 24-h fat oxidation rates as compared with lean controls who have never been obese. Consistent with this notion, longitudinal studies in Pima Indians in Arizona have shown that those with low fat oxidation rates have a greater risk of gaining body weight over time, compared with high-fat oxidizers (Zurlo et al., 1990). A reduced ability to adjust fat oxidation to homeostatic signals, which has been de ned as metabolic in exibility of substrate oxidation, is an important characteristic of obesity and insulin resistance and may possibly be associated with reductions in mitochondrial content and/or function (Ukropcova et al., 2007). Thus, the impaired ability to oxidize fat may translate into a positive energy balance over time, possibly by affecting thermogenesis and/or by affecting energy intake. Further studies will be needed to clarify the underlying mechanisms.

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