Mechanism of renal phosphate retention during growth

Mechanism of renal phosphate retention during growth. We have previously demonstrated that the retention of phosphate required for growth is due to a a high Vmax of the Na+-Pi cotransport system located in the brush border membrane of the proximal tubule. Because of this and other similarities between adaptation of the kidney to a high Pi demand (growth) and that to low Pi supply, we measured the levels of NaPi-2 mRNA and cDNA present in kidney cortex of 3- and > 12-week-old rats. Like in Pi depletion, Western blots revealed that a 80 to 85kDa protein recognized by a polyclonal antibody directed against the N-terminal region of the NaPi-2 protein was 2.3-fold more abundant in renal microvilli of the young than of adult animals. However, unlike in Pi depletion, Northern blot analysis failed to reveal a significant difference between mRNA levels at the two ages. Furthermore, suppression of NaPi-2 mRNA activity by annealing with antisense oligomers, or removal of the NaPi-2 transcripts by subtractive hybridization did not affect the rate of Na+-Pi cotransport induced in oocytes by polyA RNA of rapidly growing animals, while abolishing the ability of the renal cortical polyA RNA of adult rats to encode for Na+-Pi cotransport. RT-PCR of subtracted polyA RNA using primers specific for a region conserved in NaPi type II (Pi modulated) cotransporters yielded a product that was 98% homologous with that region, despite the absence of NaPi-2 cDNA. The results of these experiments demonstrate that the polyA RNA from kidneys of young animals contains unique mRNA transcripts able to encode for a NaPi protein homologous to, but distinct from NaPi-2

Body fat MRS

The increasing levels of obesity, and its associated comorbidities, have prompted a reassessment of the techniques used for assessing body fat, including content, distribution, and composition. Magnetic resonance spectroscopy (MRS) is one among the many invaluable in vivo tools available today to evaluate the role of body fat in health and disease. However, although MRS has become a powerful technique for assessing ectopic fat in vivo, it has had limited use in other areas of research associated with body fat. MRS has found some success as a fast method to determine whole body adiposity in rodent models of disease, as well as a noninvasive method of obtaining an index of the overall composition of body fat in human subjects. Its more significant use has been in the understanding of bone marrow fat content, where important advances have been made, especially in longitudinal studies. In conclusion, in the area of body fat, MRS continues to be an adjunct technique to more precise and versatile MRI methods

Apoptosis of Inflammatory Cells in Immune Control of the Nervous System: Role of Glia

Normal individuals have T lymphocytes capable of reacting to central nervous system (CNS) antigens such as myelin basic protein (MBP) (Martin et al., [1990]). In view of recent evidence indicating that T cells are much more cross-reactive than previously thought (Mason, [1998]), it is likely that these autoreactive T cells are often primed by exposure to cross-reacting environmental antigens. Indeed it has been shown that viral and bacterial peptides can activate myelin-reactive human T cells (Wucherpfennig and Strominger, [1995]; Hemmer et al., [1997]). Furthermore, normal healthy subjects experience surges of increased frequencies of circulating myelin-reactive T cells that might be driven by cross-reactive environmental antigens (Pender et al., [2000]). Such activated myelin-reactive T cells would be expected to enter the CNS in healthy individuals, because activated T cells of any specificity, including autoreactive T cells, enter the normal CNS parenchyma (Wekerle et al., [1986]; Hickey et al., [1991]). If CNS-reactive T cells survive in the CNS, they have the potential to attack the CNS, either directly or through the recruitment of other inflammatory cells, and thus lead to CNS damage such as demyelination. Therefore, the physiological control of autoreactive T cells in the CNS is likely to have an important role in preventing the development of autoimmune CNS disorders such as multiple sclerosis (MS) (Pender, [1998]). T-cell apoptosis in the CNS has been proposed to be an important mechanism for controlling autoimmune attacks on the CNS (Pender et al., [1992]; Schmied et al., [1993]). Although other mechanisms, such as immune deviation (Wenkel et al., [2000]), may possibly also contribute to the control of the immune response in the CNS, this review will focus on T-cell apoptosis in the CNS and the role of glia in this process

Lactate::fueling the fire starter

It is becoming increasingly appreciated that intermediates of metabolic pathways, besides their anabolic and catabolic functions, can act as signaling molecules and influence the outcome of immune responses. Although lactate was previously considered as a waste product of glucose metabolism, accumulating evidence has highlighted its pivotal role in regulating diverse biological processes, including immune cell polarization, differentiation and effector functions. In addition, lactate is a key player in modulating tumor immune surveillance. Hence, targeting lactate-induced signaling pathways is a promising tool to reduce inflammation, to prevent autoimmunity and to restore anti-tumor immune response. This article is characterized under: Biological Mechanisms > Metabolism

Sodium-coupled Monocarboxylate Transporters in Normal Tissues and in Cancer

SLC5A8 and SLC5A12 are sodium-coupled monocarboxylate transporters (SMCTs), the former being a high-affinity type and the latter a low-affinity type. Both transport a variety of monocarboxylates in a Na+-coupled manner. They are expressed in the gastrointestinal tract, kidney, thyroid, brain, and retina. SLC5A8 is localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to neurons and the retinal pigment epithelium. The physiologic functions of SLC5A8 include absorption of short-chain fatty acids in the colon and small intestine, reabsorption of lactate and pyruvate in the kidney, and cellular uptake of lactate and ketone bodies in neurons. It also transports the B-complex vitamin nicotinate. SLC5A12 is also localized to the apical membrane of epithelial cells lining the intestinal tract and proximal tubule. In the brain and retina, its expression is restricted to astrocytes and Müller cells. SLC5A8 also functions as a tumor suppressor; its expression is silenced in tumors of colon, thyroid, stomach, kidney, and brain. The tumor-suppressive function is related to its ability to mediate concentrative uptake of butyrate, propionate, and pyruvate, all of which are inhibitors of histone deacetylases. SLC5A8 can also transport a variety of pharmacologically relevant monocarboxylates, including salicylates, benzoate, and γ-hydroxybutyrate. Non-steroidal anti-inflammatory drugs such as ibuprofen, ketoprofen, and fenoprofen, also interact with SLC5A8. These drugs are not transportable substrates for SLC5A8, but instead function as blockers of the transporter. Relatively less is known on the role of SLC5A12 in drug transport

Is Overweight in Stunted Preschool Children in Cameroon Related to Reductions in Fat Oxidation, Resting Energy Expenditure and Physical Activity?

Recent studies suggest that early modifications in metabolic pathways and behaviour, leading to energy conservation and reduced linear growth, could represent adaptations to nutritional constraints during foetal life and infancy. Impaired fat oxidation, low resting energy expenditure and reduced physical activity, resulting from these adaptations, could facilitate fat storage and development of overweight in growth-retarded children that consume more energy-dense food. This study aims at assessing whether: (1) dual-burden preschool children (simultaneously stunted and overweight) of Yaounde (Cameroon) have low birth-weight (indicator of foetal undernutrition) and reductions in fat oxidation, resting energy expenditure (REE) and physical activity, (2) fat oxidation, REE and physical activity are associated with foetal growth.162 children (24-72 months) were considered: 22 stunted-overweight (SO), 40 stunted (S), 41 overweight (O), and 59 non stunted-non overweight (NSNO). Nutritional status and body composition were assessed using anthropometry and multifrequency bioimpedance analysis. Fasting respiratory quotient (RQ) and REE were measured by indirect calorimetry. Physical activity was determined using accelerometers, food questionnaires were used for diet assessment and birth-weight was noted. Mean RQs and REE (weight adjusted) did not differ between stunted children (SO and S) and non-stunted children (O and NSNO). SO and S children spent more time in sedentary activities than O children (p = 0.01 and p = 0.02, respectively) and less time in moderate-to-vigorous activities than NSNO children (p = 0.05 and p = 0.04, respectively). SO children's diet was less diverse (p = 0.01) with less animal products (p = 0.006). Multiple linear regressions model revealed that birth-weight is predictive of RQ (β = 0.237, p<0.01, R(2) = 0.08).This study showed that growth retardation in stunted-overweight children could be associated with postnatal nutritional deficiencies. Overweight in stunted children could be associated with reduced physical activity in the context of nutrition transition. High birth-weight was a predictor of reduced lipid oxidation, a risk factor of fat deposition

Reduced rate of fat oxidation: A metabolic pathway to obesity in the developing nations

The purpose of this article is to document the metabolic and environmental factors associated with the increased frequency of obesity in the developing nations. While the prevalence of obesity in the developed countries is caused by the increased consumption of calorie-dense foods, in the developing nations, because obesity coexists with undernutrition, additional factors are necessary to account for it. The evidence suggests that an important contributing factor for obesity in the developing nations is a reduced fat oxidation and increased metabolism of carbohydrate that has been brought about by the chronic undernutrition experienced during prenatal and postnatal growth. This shift toward a preferential metabolic use of carbohydrate rather than of fat results in an increased deposition of body fat. This tendency, along with the general decrease of energy expenditure in physical activity associated with urbanization, and the culturally mediated acceptance of fatness leads to obesity among populations from the developing nations. A joint effect of these factors is that in the developing nations obesity is associated with short stature resulting from developmental undernutrition, while in the developed countries obesity is associated with tall stature. It is hoped that future research will address the mechanisms whereby undernutrition increases the tendency toward obesity. Understanding how to modify fat oxidation could affect our ability to prevent weight gain among undernourished populations of the developing nations. Therefore, future research on the interaction of undernutrition and the development of obesity is of prime importance for anthropology concerned with the origins of human variability. Am. J. Hum. Biol. 15:522–532, 2003. © 2003 Wiley-Liss, Inc.Peer Reviewedhttp://deepblue.lib.umich.edu/bitstream/2027.42/35103/1/10191_ftp.pd