Characterization and localization of leptin receptors in the rat kidney

Gal, Claudine Serradeil–Le; Raufaste, Danielle; Brossard, Gabrielle; Pouzet, Brigitte; Marty, E.; Maffrand, Jean‐Pierre; Fur, G. Le

doi:10.1016/s0014-5793(97)00125-7

Cited by 115 publications

(83 citation statements)

References 37 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…It has been shown that leptin may act directly as a renal growth and fibrogenic factor, stimulating proliferation of glomerular endothelial cells and collagen production in mesangial cells. 13,21 The fact that the latter effect occurred in db/db mouse mesangial cells, which lack the functional long form of the leptin receptor (ob.R L ), and that abundant short leptin receptor isoform (ob.R s ) is detected in abundance in kidney tissue 22 suggests that the direct effects of leptin on the kidney are mediated via ob.R s . Leptin has also been shown to directly increase diuresis and natriuresis without altering blood pressure or potassium excretion.…”

Section: Discussionmentioning

confidence: 99%

Leptin induces rat glomerular mesangial cell hypertrophy, but does not regulate hyperplasia or apoptosis

2005

View full text Add to dashboard Cite

OBJECTIVE: There is an increased incidence of renal glomerulosclerosis in obese individuals. One of the major structural changes observed in nephropathy is the increase in kidney size, which may occur due to hypertrophy or changes in the rate of hyperplasia or apoptosis. Here we investigated whether leptin, the product of the obese (ob) gene which is found at high plasma levels in obese and diabetic individuals, alters any of these parameters. RESULTS: We show that leptin increased hypertrophy of these cells. This was indicated by an approximately 33% increase in cell size and 40% increase in leucine incorporation. Furthermore, we show that the hypertrophic effect of leptin was mediated via PI 3-kinase and ERK1/2 by using the inhibitors LY294002 and PD98059, respectively. We also confirm that leptin activates both PI 3-kinase and ERK1/2 in these cells. We show that hyperplasia was not affected by leptin by measuring rat glomerular mesangial cell number and by assessing bromodeoxyuridine uptake. Leptin also did not alter caspase 3-like activity under control conditions or upon induction of apoptosis by ultraviolet light, suggesting that apoptosis was not regulated by leptin in these cells. CONCLUSION: Our results show that leptin induced glomerular mesangial cell hypertrophy via PI 3-kinase and ERK1/2, and that hyperplasia and apoptosis were not altered by leptin. The hypertrophic effect of leptin may play a role in the pathophysiology of nephropathy associated with obesity.

show abstract

Section: Discussionmentioning

confidence: 99%

Leptin induces rat glomerular mesangial cell hypertrophy, but does not regulate hyperplasia or apoptosis

2005

View full text Add to dashboard Cite

show abstract

“…Therefore, disappearance in vivo of a possible direct inhibitory effect of insulin on renal gluconeogenesis in our diabetic rats, which are known to be insulinopenic at 14 to 17 wk of age, was probably not involved in the intrinsic stimulation of in vitro renal gluconeogenesis that we observed in these rats. It also should be pointed out that leptin resistance, which is characteristic of our diabetic rats, could not be involved in the effects observed because leptin receptors in the rat kidneys are localized exclusively in the renal inner medulla (36). Similarly, glucagon, whose plasma levels have been shown to be elevated in patients with type 2 diabetes (37), was probably not involved directly in the stimulation of renal gluconeogenesis, because this hormone does not stimulate the production of cAMP in the renal proximal tubule (38).…”

Section: Factors Responsible For Long-term Stimulation Of Renal Glucomentioning

confidence: 93%

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

Eid

Bodin²,

Ferrier³

et al. 2006

Journal of the American Society of Nephrology

View full text Add to dashboard Cite

Recent studies indicate that renal gluconeogenesis is substantially stimulated in patients with type 2 diabetes, but the mechanism that is responsible for such stimulation remains unknown. Therefore, this study tested the hypothesis that renal gluconeogenesis is intrinsically elevated in the Zucker diabetic fatty rat, which is considered to be an excellent model of type 2 diabetes. For this, isolated renal proximal tubules from diabetic rats and from their lean nondiabetic littermates were incubated in the presence of physiologic gluconeogenic precursors. Although there was no increase in substrate removal and despite a reduced cellular ATP level, a marked stimulation of gluconeogenesis was observed in diabetic relative to nondiabetic rats, with near-physiologic concentrations of lactate (38%), glutamine (51%) and glycerol (66%). This stimulation was caused by a change in the fate of the substrate carbon skeletons resulting from an increase in the activities and mRNA levels of the key gluconeogenic enzymes that are common to lactate, glutamine, and glycerol metabolism, i.e., mainly of phosphoenolpyruvate carboxykinase and, to a lesser extent, of glucose-6-phosphatase and fructose-1,6-bisphosphatase. Experimental evidence suggests that glucocorticoids and cAMP were two factors that were responsible for the long-term stimulation of renal gluconeogenesis observed in the diabetic rats. These data provide the first demonstration in an animal model that renal gluconeogenesis is upregulated by a long-term mechanism during type 2 diabetes. Together with the increased renal mass (38%) observed, they lend support to the view so far based only on in vivo studies performed in humans that renal gluconeogenesis may be stimulated by and crucially contribute to the hyperglycemia of type 2 diabetes.

show abstract

“…In mature kidneys, five isoforms of the leptin receptors are known to be active and these are mainly located in the inner medullar (34) . In vivo studies demonstrate that leptin can regulate Na handling and increase renal sympathetic nerve activity, which are early signs of hypertension (35,36) .…”

Section: The Role Of Leptinmentioning

confidence: 99%

The conflicting effects of maternal nutrient restriction and early-life obesity on renal health

Fainberg

Budge²,

Symonds³

2011

Proc. Nutr. Soc.

View full text Add to dashboard Cite

Epidemiological and animal studies have demonstrated that early-life nutrition alters the metabolic responses and generates structural changes in complex tissues, such as the kidneys, which may lead to a reduction in the offspring lifespan. Independently, obesity induces a spontaneous low-grade chronic inflammatory response by modulating several of the major metabolic pathways that ultimately compromise long-term renal health. However, the combined effects of maternal nutrition and early-life obesity in the development of renal diseases are far from conclusive. Previous results, using the ovine model, demonstrated that the combination of a reduction in fetal nutrition and juvenile obesity induced a series of adaptations associated with severe metabolic syndrome in the heart and adipose tissue. Surprisingly, exposure to an obesogenic environment in the kidney of those offspring produced an apparent reduction in glomerulosclerosis in relation to age-and weight-matched controls. However, this reduction in cellular apoptosis was accompanied by a rise in glomerular filtration rate and blood pressure of equal intensity when compared with obese controls. The intention of this review is to explain the adaptive responses observed in this model, based on insights into the mechanism of renal fetal programming, and their potential interactions with some of the metabolic changes produced by obesity. Maternal nutrient restriction: Renal health: Fetal programmingDeterioration in renal health is the result of both heritable and environmental factors which, in turn, influence the rate of functional decline. A clear environmental factor that reduces kidney function is that produced with chronic inflammation and induced by metabolic disorders, such as obesity (1,2) . A good example of the intricate relationship between the nutritional environment and metabolic-renalassociated diseases at the population level is observed in previously underdeveloped countries, such as China, a society that has experienced rapid growth in the prevalence of obesity due to several changes in lifestyle (3) . In less than a generation, medical conditions associated with overweight or obesity, including type 2 diabetes, hypertension and renal diseases, have increased to unprecedented levels, matching those existing in western developed countries. Unfortunately, this rapid change in the nutritional environment has exposed an inherent human vulnerability to the complications of excess weight gain particularly in young children (3) . In an attempt to explain the effects of early-life nutrition observed in previous epidemiological studies and their association with the development of metabolic complications in later life, Barker and Hales proposed the 'thrifty phenotype hypothesis' (4) . The basis of this hypothesis is that the maternal nutritional environment and early postnatal life nutrition play a major role in the pathogenesis of Abbreviations: GH, growth hormone; IGF, insulin-like growth factor; RAS, renin-angiotensin system.

show abstract

Characterization and localization of leptin receptors in the rat kidney

Cited by 115 publications

References 37 publications

Leptin induces rat glomerular mesangial cell hypertrophy, but does not regulate hyperplasia or apoptosis

Leptin induces rat glomerular mesangial cell hypertrophy, but does not regulate hyperplasia or apoptosis

Intrinsic Gluconeogenesis Is Enhanced in Renal Proximal Tubules of Zucker Diabetic Fatty Rats

The conflicting effects of maternal nutrient restriction and early-life obesity on renal health

Contact Info

Product

Resources

About