Differential Expression of Leptin Receptor in High‐ and Low‐Fat‐Fed Osborne‐Mendel and S5B/Pl Rats

Madiehe, Abram Madimabe; Schaffhauser, Andrea O.; Braymer, Douglas; Bray, George A.; York, David A.

doi:10.1038/oby.2000.58

Cited by 58 publications

(41 citation statements)

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“…50 Other authors did not find significant changes in OB-Rb mRNA levels in the hypothalamus of Wistar rats fed with HF diet, 48 or in two rat strains with different susceptibility to becoming obese when exposed to dietary manipulations, the Osborne-Mendel (OM) rats (susceptible) and the S5B/P1 rats (highly resistant). 51 However, in these latter rat strains (OM and S5B/P1), receptor protein levels (both the short and the long form) were downregulated after 14 days HF diet feeding. 51 SOCS-3 is a leptin-inducible inhibitor of leptin signalling, and a potential mediator of leptin resistance in obesity.…”

Section: Discussionmentioning

confidence: 91%

“…51 However, in these latter rat strains (OM and S5B/P1), receptor protein levels (both the short and the long form) were downregulated after 14 days HF diet feeding. 51 SOCS-3 is a leptin-inducible inhibitor of leptin signalling, and a potential mediator of leptin resistance in obesity. 52 Of interest, we found significantly lower SOCS-3 mRNA levels in leptin-treated animals than in their untreated controls both under NF (45% reduction) or HF diet (31% reduction).…”

Section: Discussionmentioning

confidence: 91%

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The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

et al. 2007

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Ciber Fisiopatología obesidad y nutrición (CB06/03) Instituto Salud Carlos III, SpainBackground: There is epidemiological evidence that perinatal nutritional factors may have long-term effects on obesity. Which nutrients or food components are involved in this programming mechanism are unknown. Breast milk contains leptin, a hormone that regulates food intake and energy expenditure, and previous studies in rats have shown that leptin orally administered during lactation exerts anorexigenic effects. Objective: To evaluate whether supplementation with physiological doses of oral leptin during lactation has long-term effects on body weight regulation. Design: A daily oral dose of leptin (equivalent to five times the amount of leptin ingested normally from maternal milk during the suckling period) or the vehicle was given to suckling male rats during lactation. Animals were fed after weaning with a normal fat (NF) or a high-fat (HF) diet. We followed body weight and food intake of animals until the age of 6 months, and measured the size of adipose tissue depots, the thermogenic capacity, the expression of leptin in the stomach and adipose tissues and the expression of two appetite-related peptides (neuropeptide Y (NPY) and proopiomelanocortin (POMC)), leptin receptor (OB-Rb) and suppressor of cytokine signalling 3 (SOCS-3) in the hypothalamus at the age of 6 months. Results: Leptin-treated animals had, in adulthood, lower body weight and fat content and ate fewer calories than their untreated controls. Unlike adipocitary leptin production, adult animals that were leptin-treated during lactation displayed higher gastric leptin production without changes in OB-Rb mRNA levels. In addition, in response to HF diet, leptin-treated animals (contrary to controls) showed lower hypothalamic NPY/POMC mRNA ratio. Hypothalamic OB-Rb mRNA levels decreased in control animals as an effect of HF diet feeding, but remained unchanged in leptin-treated animals; SOCS-3 mRNA levels were lower in leptin-treated animals than in their controls, both under normal or HF diet. Conclusion: The animals that received leptin during lactation become more protected against fat accumulation in adult life and seem to be more sensitive to the short-and long-term regulation of food intake by leptin. Thus, leptin plays an important role in the earlier stages of neonatal life, as a component of breast milk, in the prevention of later obesity.

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Section: Discussionmentioning

confidence: 91%

Section: Discussionmentioning

confidence: 91%

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

et al. 2007

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“…By western blotting, we detected an immunoreactive band at approximately 118 kDa using the short-form speci®c (ObR K-20, Santa Cruz Biotechnology) leptin receptor antibody (see also (43)). This was the only major band detected.…”

Section: Protein Expression Of Obr-s Is Up-regulated By Maternal Dexamentioning

confidence: 99%

Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

Sugden

Langdown²,

Munns³

et al. 2001

European Journal of Endocrinology

120

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Background: Leptin concentrations are increased during late pregnancy, and leptin receptors are expressed in placental and fetal tissues, suggesting a role for leptin in placental and/or fetal growth, or both. In humans, leptin concentrations in adulthood are inversely related to body weight at birth, independent of adult adiposity, and correlate with fasting insulin. Glucocorticoids and insulin regulate leptin secretion. Excessive exposure to glucocorticoids during late fetal development in the rat causes intrauterine growth retardation (IUGR), together with hypertension and hyperinsulinaemia in adulthood. Leptin may have a role in the development of some forms of hypertension. Objective: To determine whether IUGR induced by maternal glucocorticoid treatment during the last third of pregnancy in the rat is associated with modulation of either maternal or fetal leptin concentrations, the placental expression of leptin or the short form of the leptin receptor (ObR-S), or combinations thereof, and to evaluate whether hypertension or hyperinsulinaemia in the earlygrowth-retarded adult progeny of dexamethasone-treated dams is associated with altered leptin concentrations. Design and Methods: Dexamethasone was administered to pregnant rats from day 15 to day 21 of gestation via a chronically implanted subcutaneous osmotic minipump. Protein expression of leptin and ObR-S in the placenta at day 21 of pregnancy was measured by western blotting. Plasma leptin and insulin concentrations were determined by radioimmunoassay and ELISA respectively. Systolic hypertension was measured by tail cuff plethysmography. Results: Dexamethasone administration during the last third of pregnancy decreased placental mass and fetal body weight at day 21 of gestation, caused maternal hyperleptinaemia but fetal hypoleptinaemia, and suppressed placental leptin protein expression whilst up-regulating placental protein expression of ObR-S. The male and female offspring of dexamethasone-treated dams were hypertensive from 12 weeks of age. One-year-old offspring of dexamethasone-treated dams exhibited signi®cant hyperleptinaemia compared with age-matched controls, an effect associated with hyperinsulinaemia in the male, but not female, offspring. Conclusions: The rat model of maternal dexamethasone treatment is established as a paradigm of programmed' hypertension in man. Our data show modi®cation of placental leptin and leptin receptor protein expression by dexamethasone treatment during the last third of pregnancy. We also show that leptin concentrations are suppressed during fetal life but increased in adulthood in this rat model of programmed hypertension. Our data do not necessarily establish a causal relationship between fetal hypoleptinaemia and impaired fetal growth during early life, or between hyperleptinaemia and hypertension in adulthood. Nevertheless, they suggest that hyperleptinaemia may be a component of the cluster of metabolic abnormalities seen in the insulin resistance syndrome in man. They also suggest that excessive...

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“…More careful behavioral analysis of the sequence of events in the induction of diet-induced leptin resistance revealed what appeared to be a two-step process over successive weeks of HF feeding, with the expression of first peripheral, and then central, leptin resistance (23, 39). Parallel work on potential biological mechanisms underlying leptin resistance revealed the saturation at elevated circulating leptin levels of an active blood-brain barrier (BBB) leptin transport mechanism (7, 12), reduced hypothalamic leptin receptor expression (42,66), and the inhibition of hypothalamic leptin receptor signal transducer and activator of transcription-3 (STAT-3) second messenger signaling (23) in HF-fed animals. Evidence indicates that these biological events may well parallel the behavioral sequence described above in the induction of leptin resistance (23, 38).…”

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confidence: 99%

Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance. Focus on “Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding,” by Shapiro et al.

Vasselli¹

2008

American Journal of Physiology-Regulatory, Integrative and Comp

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Brief Historical PerspectiveTHE CONCEPT OF LEPTIN RESISTANCE appeared in the literature almost as soon as the hormone itself was discovered. For purposes of our discussion, leptin resistance will be defined as, "reduced or absent responsiveness to the feeding and body weight inhibitory effects of the hormone in obese individuals in comparison with normal (lean) controls." Two early reports, demonstrating significant correlations in humans between circulating leptin levels and increasing adiposity, came to the conclusion that resistance to the purported regulatory role of leptin on appetite and body weight must be induced as levels of the hormone increase (18,43). In short order, the concept of leptin resistance was given experimental support by the finding of decreased ratios of cerebrospinal fluid vs. plasma levels of leptin in obese humans (14,61). Parallel findings were made at almost the same time in obese rodents (24,73). Whatever its mechanism, the notion of leptin resistance provided a ready explanation for excess body fat in individuals in the face of extremely high circulating leptin levels. Despite rather compelling initial observations, the notion of leptin resistance remained controversial at early stages of its advancement (4), or was reinterpreted in terms of individual variability in genetically determined leptin response thresholds (56). In fairness, these reviews appeared prior to experimental evidence demonstrating the existence of leptin resistance in obese humans (28,31,44). Moreover, findings of significant associations between leptin receptor gene polymorphisms and body mass index, fat mass, and eating behavior in humans were subsequently published (15, 21, 69). Nevertheless, it was not until experimental demonstrations of the phenomenon in outbred animals and subsequent analyses of the biological mechanisms involved that the notion gained widespread acceptance.Experimental leptin resistance was first demonstrated in wild-type mice made obese on a high-fat (HF) diet (13). This was followed by numerous reports of leptin resistance in diet-induced obese rodent models in response to central and/or peripheral administration of leptin (25,70,72). More careful behavioral analysis of the sequence of events in the induction of diet-induced leptin resistance revealed what appeared to be a two-step process over successive weeks of HF feeding, with the expression of first peripheral, and then central, leptin resistance (23, 39). Parallel work on potential biological mechanisms underlying leptin resistance revealed the saturation at elevated circulating leptin levels of an active blood-brain barrier (BBB) leptin transport mechanism (7, 12), reduced hypothalamic leptin receptor expression (42,66), and the inhibition of hypothalamic leptin receptor signal transducer and activator of transcription-3 (STAT-3) second messenger signaling (23) in HF-fed animals. Evidence indicates that these biological events may well parallel the behavioral sequence described above in the induction of leptin resistance (23, ...

show abstract

Differential Expression of Leptin Receptor in High‐ and Low‐Fat‐Fed Osborne‐Mendel and S5B/Pl Rats

Cited by 58 publications

References 56 publications

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

The intake of physiological doses of leptin during lactation in rats prevents obesity in later life

Maternal glucocorticoid treatment modulates placental leptin and leptin receptor expression and materno-fetal leptin physiology during late pregnancy, and elicits hypertension associated with hyperleptinaemia in the early-growth-retarded adult offspring

Fructose-induced leptin resistance: discovery of an unsuspected form of the phenomenon and its significance. Focus on “Fructose-induced leptin resistance exacerbates weight gain in response to subsequent high-fat feeding,” by Shapiro et al.

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