Leptin, the product of the ob gene, controls appetite through the hypothalamus and may affect many other tissues because of the widespread distribution of its receptors. Leptin is synthesized by white adipose tissue (WAT) under conditions of high energy availability and insulin stimulus. Glucocorticoids enhance this synthesis and catecholamines hamper leptin production. Leptin diminishes insulin secretion by the pancreatic beta cells and induces insulin resistance. In fact leptin hampers insulin action on WAT itself in a negative feedback loop. The evidence acquired in studies on diabetics, starvation, refeeding and insulin and glucose clamps supports this interpretation, which may also explain part of the difficulties encountered by the current postulate that links leptin to WAT mass size signalling to the brain. Leptin may be, essentially, a counter-regulatory hormone limiting the insulin drive to store energy in the form of fat, its effects reaching from a decrease in food intake to lower insulin secretion and increased resistance to insulin and lower glucose uptake and fat synthesis by WAT.Key words: Leptin; Insulin; Obesity Leptin expression in white adipose tissueThe study of the mechanisms controlling body weight has received an enormous boost during the last year thanks to the identification of the ob gene and its product, leptin, which induces the loss of fat in ob/ob mice [1][2][3]. Leptin is expressed only in adipose tissues [4], though it is more intensely expressed in white than in brown adipose tissue [5].The gene db, encoding the leptin receptor has been characterized in mice [6], and in rats, where it has been found to coincide with the fa mutation [7]; its defect results in the overexpression of the ob gene [8]. Leptin down-regulates the expression of the ob gene via paracrine or endocrine pathways, since isolated adipocytes do not respond to direct leptin stimulation [9]. Sympathetic activity or cAMP lowers the expression of the ob gene [9]. In white adipose tissue, ß-adrenergic stimulation decreases ob gene expression [5]. Cold exposure, directly related to sympathetic stimulation rewarming, also lowers the synthesis of leptin in adipose tissue, an effect that can be partially reversed by reheating [10].In vivo leptin release by adipose tissue has been demonstrated in humans and circulating leptin levels are correlated with degree of obesity [11], because of overexpression of the ob gene [12]. Leptin and insulin levels, as well as body weight, are inter-correlated [13]. However, non-insulin-dependent *Corresponding author. Fax: (34) (3) 4021559. E-mail: remesar@porthos.bio.ub.es diabetics show leptin levels which do not differ from those of non-diabetic humans of the same body mass index [14].In normal rats, ob gene expression is down-regulated by insulinemia under euglycemic conditions [15]. The presence of insulin is also required for leptin release [16]. In streptozotocin-diabetic rodents, however, the low levels of ob gene mRNA are not fully restored with continuous insulin treatm...
The amino acid composition of the protein from three strains of rat (Wistar, Zucker lean and Zucker obese), subjected to reference and high-fat diets has been used to determine the mean empirical formula, molecular weight and N content of wholerat protein. The combined whole protein of the rat was uniform for the six experimental groups, containing an estimate of 17.3% N and a mean aminoacyl residue molecular weight of 1037. This suggests that the appropriate protein factor for the calculation of rat protein from its N content should be 5.77 instead of the classical 6.25. In addition, an estimate of the size of the non-protein N mass in the whole rat gave a figure in the range of 5.5 ' YO of all N. The combination of the two calculations gives a protein factor of 5.5 for the conversion of total N into rat protein.Nitrogen conversion factor (6.25) : Protein analysis: Protein nitrogen : RatThe enormous variety of different protein species that can be found in a complex living organism is a severe handicap for their global measurement. The different physical and chemical properties of such a large array of molecules, having in common only their amino acid building blocks and the peptide bonds joining them, lead to serious difficulties in their estimation as a class of compounds.In N and nutrient energy balance studies the analytical needs are focused on the estimation of 'protein' as a differentiated entity comprising myriads of, often very different, individual protein species at varying concentrations. Most methods used for the undifferentiated estimation of 'protein' are necessarily crude in their approach, which invariably limits their precision and uniformity of application. The most favoured method is the time-honoured measurement of all N contained in the sample by means of a Kjeldahl digestion or using elemental analysers, and multiplying the result obtained by a factor depending on the N content of the protein. The factor of 6.25 for the conversion of N values to protein values has been in use for most of this century in spite of its obscure origins (Hiller et al. 1948) and is still commonly applied in such balances despite its known variability (Passmore & Eastwood, 1986). The differences between protein sources as uniform in their composition as dairy or wheat products have urged the application of other N-to-protein factors (Lloyd et al. 1978).The applicability of the 6.25 factor has been discussed (Hiller et al. 1948;Lloyd et al.
The content and accretion of fatty acids in 30, 45 and 60-day old Wistar rats fed either reference chow or a cafeteria diet has been studied, together with their actual fatty acid intake during that period. Diet had a small overall effect on the pattern of deposition of fatty acids, but the deposition of fat was much higher in cafeteria rats. The fat-rich cafeteria diet allowed the direct incorporation of most fatty acids into lipid storage, whilst chow-feeding activated lipogenesis and the deposition of a shorter chain and more saturated type of fatty acids. During the second month of the rat's life, the elongation pathway as well as delta 9-desaturase became functional, thus helping to shape the pattern of fatty acids actually accrued. The 60-day rats showed a relative impairment in the operation of delta 5-desaturase, since their lipids had a higher C20:4/C20:3 ratio than those of the diet ingested. Cafeteria-diet feeding minimized this effect since the large supply of dietary polyunsaturated fatty acids made the operation of the elongation-desaturase pathways practically unnecessary.
The amino acid composition of the diet ingested by reference and cafeteria diet-fed lean and obese Zucker rats has been analyzed from day 30 to 60 after birth. Their body protein amino acid composition was measured, as well as the urinary and faecal losses incurred during the period studied. The protein actually selected by the rats fed the cafeteria diet had essentially the same amino acid composition as the reference diet. The mean protein amino acid composition of the rat showed only small changes with breed, age or diet. Cafeteria-fed rats had a higher dietary protein digestion/absorption efficiency than reference diet-fed rats. Obese rats wasted a high proportion of dietary amino acids when given the reference diet, but not on the cafeteria diet. In all cases, the amino acids lost as such in the urine were a minimal portion of available amino acids. In addition to breed, the rates of protein accretion are deeply influenced by diet, but even more by the age-or size-of the animals: cafeteria-fed rats grew faster, to higher body protein settings, but later protein accrual decreased considerably; this is probably due to a limitation in the 'blueprint for growth' which restricts net protein deposition when a certain body size is attained. Obese rats, however, kept accruing protein with high rates throughout. Diet composition--and not protein availability or quality--induced deep changes in amino acid metabolism. Since the differences in the absolute levels of dietary protein or carbohydrate energy ingested by rats fed the reference or cafeteria diets were small, it can be assumed that high (lipid) energy elicits the changes observed in amino acid metabolism by the cafeteria diet. The effects induced in the fate of the nitrogen ingested were more related to the fractional protein energy proportion than to its absolute values. Cafeteria-fed rats tended to absorb more amino acids and preserve them more efficiently; these effects were shown even under conditions of genetic obesity. There were deep differences in handling of dietary amino acids by dietary or genetically obese rats. The former manage to extract and accrue larger proportions of their dietary amino acids than the latter. The effects of both 'models' of amino acid management were largely additive, suggesting that the mechanisms underlying the development of obesity did not run in parallel to those affecting the control of amino acid utilization. Obesity may be developed in both cases despite a completely different strategy of amino acid assimilation, accrual and utilization.
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