A Protein-Stat Mechanism for Regulation of Growth and Maintenance of the Lean Body Mass

Dj, Millward

doi:10.1079/nrr19950008

Cited by 102 publications

(92 citation statements)

References 67 publications

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“…The question is: at what point does this loss begin to matter in functional terms? I agree with Millward's suggestion that there is probably a set-point or upper limit to the LBM, beyond which it will not increase, however high the protein intake (Millward, 1995), just as there appears to be an upper limit for albumin or haemoglobin concentration. But below this limit there must be a range of levels of LBM that are adequate or acceptable.…”

Section: Protein Metabolism ð Possible Adaptationssupporting

confidence: 83%

The nature and significance of nutritional adaptation

Waterlow

1999

Eur J Clin Nutr

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Possible adaptations to a low protein intake are: a decrease in the obligatory nitrogen loss, which would be too small to detect in short-term studies, but would be signi®cant over a longer term; an increase in the ef®ciency of protein utilization, which has been demonstrated in depleted subjects; and a decrease in lean body mass, mainly at the expense of muscle. However, we do not know the extent to which this last mechanism may really be an adaptation without signi®cant functional loss.In the case of energy there is controversy about the extent to which the gross ef®ciency of muscular work can be improved. One mechanism might be an alteration in the distribution of ®bre types, with a shift from fast to slow ®bres. A possible way of reducing the cost of both muscular work and basal metabolism would be a reduction in the mitochondrial proton leak. Both these mechanisms are at least partially under the control of the thyroid gland, which therefore may play an important role in economizing energy expenditure.

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Section: Protein Metabolism ð Possible Adaptationssupporting

confidence: 83%

The nature and significance of nutritional adaptation

Waterlow

1999

Eur J Clin Nutr

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“…While these findings of a link between FFM, hunger and midbrain blood flow may suggest a centrally mediated mechanism whereby EE directly drives FFM-induced energy intake, there is also fragmentary evidence suggesting that energy intake is regulated by one or more molecular signals arising from the FFM or from specific organ masses, in particular the skeletal muscle. This notion, which has formed the basis of an 'aminostatic' theory of appetite control 13,14 and a 'protein-static' control of food intake in relation to the impetus for lean tissue growth or maintenance, 15 has particular relevance when considering the dynamic phase of body weight recovery during refeeding or obesity relapse, and hence when examining the relationship between deficits in FFM and increased energy intake ( Figure 2). …”

Section: Passive Role Of Ffm In Driving Energy Intakementioning

confidence: 99%

Passive and active roles of fat-free mass in the control of energy intake and body composition regulation

et al. 2016

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While putative feedback signals arising from adipose tissue are commonly assumed to provide the molecular links between the body's long-term energy requirements and energy intake, the available evidence suggests that the lean body or fat-free mass (FFM) also plays a role in the drive to eat. A distinction must, however, be made between a 'passive' role of FFM in driving energy intake, which is likely to be mediated by 'energy-sensing' mechanisms that translate FFM-induced energy requirements to energy intake, and a more 'active' role of FFM in the drive to eat through feedback signaling between FFM deficit and energy intake. Consequently, a loss of FFM that results from dieting or sedentarity should be viewed as a risk factor for weight regain and increased fatness not only because of the impact of the FFM deficit in lowering the maintenance energy requirement but also because of the body's attempt to restore FFM by overeating-a phenomenon referred to as 'collateral fattening'. A better understanding of these passive and active roles of FFM in the control of energy intake will necessitate the elucidation of peripheral signals and energy-sensing mechanisms that drive hunger and appetite, with implications for both obesity prevention and its management. INTRODUCTIONSome 30 years ago, Gilbert Forbes pointed out that the lean body mass and body fat are in a sense companions, so that in many situations a change in one is accompanied by a change in the other, and usually in the same direction. 1 Until recently, however, the extent to which the lean body or fat-free mass (FFM) component in this companionship influences energy intake has been largely ignored, amid a dominant adipocentric view of appetite control that has been reinforced by the discovery of leptin and its relationship with fat mass (FM).In fact, in an early investigation about the relationships between body composition and objectively measured ad libitum food intake over several weeks in obese and non-obese women, Lissner et al. 2 showed that the energy intake for the maintenance of body weight was not correlated with adiposity expressed as percent body fat or as FM, but was positively associated with FFM. These findings were ignored or overlooked for the next 25 years despite the more than 100 citations that this publication received, albeit in relation to its other important findings about under-reporting of food intake by both obese and non-obese individuals. It is only recently that the predictive power of FFM on energy intake has gained attention following the demonstration by Blundell et al. 3 that FFM, but not FM, was positively associated with self-selected meal size and total energy intake in overweight and obese subjects. Further confirmation of a positive association between energy intake with FFM, but not FM, can be derived from studies in adults 4-6 as well as in overweight and obese adolescents. 7 Taken together, these findings have strengthened the argument of Lissner et al. 2 that 'research that focuses on the relationship between ener...

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“…The upper limit of N balance is much harder to de®ne. It may well be, as Millward (1995) has suggested, that there is a protein-stat mechanism for the regulation of the LBM which includes a set-point for the skeletal muscle component which the body strives to achieve and maintain and which is physiologically and biochemically dif®cult to exceed. This is certainly the case for individual proteins such as plasma albumin and, under normal conditions, haemoglobin.…”

Section: The Physiological Evidencementioning

confidence: 99%

The mysteries of nitrogen balance

Waterlow¹

1999

Nutr. Res. Rev.

113

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The ®rst part of this review is concerned with the balance between N input and output as urinary urea. I start with some observations on classical biochemical studies of the operation of the urea cycle. According to Krebs, the cycle is instantaneous and automatic, as a result of the irreversibility of the ®rst enzyme, carbamoyl-phosphate synthetase 1 (EC 6.3.5.5; CPS-I), and it should be able to handle many times the normal input to the cycle. It is now generally agreed that acetyl glutamate is a necessary co-factor for CPS-1, but not a regulator. There is abundant evidence that changes in dietary protein supply induce coordinated changes in the amounts of all ®ve urea-cycle enzymes. How this coordination is achieved, and why it should be necessary in view of the properties of the cycle mentioned above, is unknown. At the physiological level it is not clear how a change in protein intake is translated into a change of urea cycle activity. It is very unlikely that the signal is an alteration in the plasma concentration either of total amino-N or of any single amino acid. The immediate substrates of the urea cycle are NH 3 and aspartate, but there have been no measurements of their concentration in the liver in relation to urea production. Measurements of urea kinetics have shown that in many cases urea production exceeds N intake, and it is only through transfer of some of the urea produced to the colon, where it is hydrolysed to NH 3 , that it is possible to achieve N balance. It is beginning to look as if this process is regulated, possibly through the operation of recently discovered urea transporters in the kidney and colon. The second part of the review deals with the synthesis and breakdown of protein. The evidence on whole-body protein turnover under a variety of conditions strongly suggests that the components of turnover, including amino acid oxidation, are in¯uenced and perhaps regulated by amino acid supply or amino acid concentration, with insulin playing an important but secondary role. Molecular biology has provided a great deal of information about the complex processes of protein synthesis and breakdown, but so far has nothing to say about how they are coordinated so that in the steady state they are equal. A simple hypothesis is proposed to ®ll this gap, based on the self-evident fact that for two processes to be coordinated they must have some factor in common. This common factor is the amino acid pool, which provides the substrates for synthesis and represents the products of breakdown. The review concludes that although the achievement and maintenance of N balance is a fact of life that we tend to take for granted, there are many features of it that are not understood, principally the control of urea production and excretion to match the intake, and the coordination of protein synthesis and breakdown to maintain a relatively constant lean body mass.

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A Protein-Stat Mechanism for Regulation of Growth and Maintenance of the Lean Body Mass

Cited by 102 publications

References 67 publications

The nature and significance of nutritional adaptation

The nature and significance of nutritional adaptation

Passive and active roles of fat-free mass in the control of energy intake and body composition regulation

The mysteries of nitrogen balance

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