Recombinant Mouse OB Protein: Evidence for a Peripheral Signal Linking Adiposity and Central Neural Networks

Campfield, L. Arthur; Fj, Smith; Guisez, Yves; Devos, René; Burn, Paul

doi:10.1126/science.7624778

Cited by 3,033 publications

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References 24 publications

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“…21,22 This was replicated entirely by small doses of leptin administered directly into the brain, suggesting that the main effect of leptin was to act as a signal from adipose tissue to the brain regarding the quantity of fat tissue stored. 23 Jeff Flier and colleagues at the Beth Israel Hospital in Boston were the first to elegantly show that leptin was most likely to have evolved as a signal for Inheritance and human obesity S O'Rahilly and IS Farooqi starvation rather than nutrient excess, in that the rapid fall of leptin in the plasma seen upon fasting was necessary for the normal neurohormonal adaptations seen with starvation in mammals. 24 Mutations in single genes involved in the central control of energy balance can lead to human obesity At this stage in the mid-1990s, the relevance of leptin to human physiology was uncertain.…”

Section: Discussionmentioning

confidence: 99%

Human obesity as a heritable disorder of the central control of energy balance

O’Rahilly

Farooqi

2008

Int J Obes

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In the spirit of celebration associated with the 20th anniversary of the Pennington Biomedical Research Center, we have seized the opportunity of taking a highly personal and not at all comprehensive 'whistle-stop tour' of a large body of evidence that, we feel, supports the following conclusions: (1) that body fat stores are regulated by biological control processes in humans as they are in lower animals; (2) that there are major inherited influences on the efficiency whereby such control processes operate in humans; (3) that the precise nature of those genetic and biological influences and how they interact with environmental factors are beginning to be understood; (4) that most of the genes discovered thus far have their principal impact on hunger, satiety and food intake; (5) that while there is understandable resistance to the notion that genes can influence a human behavior such as the habitual ingestion of food, the implications of these discoveries are essentially benign. Indeed, we hope that they may eventually lead to improved treatment for patients and, in addition, help to inculcate a more enlightened attitude to the obese with a reduction in their experience of social and economic discrimination.

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Section: Discussionmentioning

confidence: 99%

Human obesity as a heritable disorder of the central control of energy balance

O’Rahilly

Farooqi

2008

Int J Obes

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“…2,3 Leptin signals nutritional status and energy storage levels to feeding centers, through its action on the expression and release of orexigenic and anorexigenic neuropeptides, including, respectively, neuropeptide Y (NPY) and proopiomelanocortin (POMC). 4 In the arcuate nucleus, NPY and POMC neurons express the long form of leptin receptor (OB-Rb), which is functionally coupled to the Janus kinase-signal transducer and activator of transcription intracellular signalling cascade and produces an endogenous inhibitor (suppressor of cytokine signalling 3, SOCS-3) upon activation. 5 This action prompts appropriate regulation of food intake and energy expenditure processes and helps our body to maintain the amount of fat stores within a certain range.…”

Section: Introductionmentioning

confidence: 99%

“…5 This action prompts appropriate regulation of food intake and energy expenditure processes and helps our body to maintain the amount of fat stores within a certain range. 1,2,4,6,7 However, most obese people appear to be resistant to the action of leptin. In fact, the administration of this hormone, while proven to be effective in reducing fat and normalizing metabolic disorders in leptin-deficient mice and humans, has not proven to be effective in most cases of obesity.…”

Section: Introductionmentioning

confidence: 99%

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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“…The role of adipostat is based on the strong association between leptin gene expression, circulating leptin levels, and body fat content across animals of different genotypes (Frederich et al, 1995;McDougald et al, 1995). Leptin receptors are present in the hypothalamus (Chua et al, 1996), and increases in plasma leptin concentrations have been shown to inhibit feed intake, reduce Ld, and increase metabolic rate (Campfield et al, 1995;Halaas et al, 1997). The role of leptin as an adipostat is confirmed by the increases in plasma leptin levels (Table 4; P , 0.05) at the end of the restriction phase and when AA intake was reduced.…”

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confidence: 99%

Nutrition-induced differences in body composition, compensatory growth and endocrine status in growing pigs ,

Martínez-Ramírez

Jeaurond

Lange

2009

Animal

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In this experiment, we assessed the effect of amino acid (AA) intake restriction in entire male Yorkshire pigs between 15 and 38 kg BW (restriction phase) on BW gain, body composition and plasma levels of blood urea nitrogen (BUN), cortisol, insulinlike growth factor I (IGF-I), growth hormone (GH) and leptin during the subsequent re-alimentation phase. During the restriction phase, 36 pigs were allotted to one of two dietary treatments: adequate AA intake (control) or AA-limiting diets (AA-30%). Thereafter, pigs were fed common non-limiting diets up to 110 kg BW. Throughout the experiment, pigs were scale-fed at 90% of the estimated voluntary daily digestible energy intake. At the end of the restriction phase, pigs on AA-30% had lesser BW gain (650 v. 784 g/day; P , 0.001), loin area (LA; 12.2 v. 14.2 cm 2 ; P , 0.001), BUN (4.6 v. 6.3 mg/dl; P , 0.02), lesser plasma levels of IGF-I (440 v. 640 ng/m; P , 0.001) and cortisol (8.2 v. 19.2 mg/dl; P , 0.001), greater backfat thickness (BF; 7.56 v. 6.56 mm; P , 0.02), and greater plasma levels of leptin (2.7 v. 1.8 ng/ml; P 5 0.027) and GH (3.3 v. 2.0 ng/ml; P 5 0.05) than pigs on control. During the re-alimentation phase, previously restricted pigs showed full compensatory growth (CG) in terms of BW gain (1170 v. 1077 g/day; P , 0.002), whole-body protein deposition (Pd) (179 v. 163 g/day; P , 0.001) as well as physical and chemical body composition (whole-body lipid to body protein mass ratio, LB/PB; 1.14 v. 1.15; P . 0.10). Besides GH at 45 kg BW (4.2 v. 2.4 ng/ml; P 5 0.066), there were no effects of previous AA intake restriction on leptin, IGF-I and BUN during the re-alimentation phase ( P . 0.10). Plasma cortisol and IGF-I levels may act as an indicator of AA-induced restriction in Pd in growing pigs. Plasma BUN level does not appear as a sensitive indicator for compensatory Pd. Plasma leptin and GH levels allow for the involvement of the brain in controlling chemical body composition. Full CG was observed during the energydependent phase of Pd in growing pigs and might be driven by a target LB/PB, possibly mediated via plasma leptin, IGF-I and GH levels.

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Recombinant Mouse OB Protein: Evidence for a Peripheral Signal Linking Adiposity and Central Neural Networks

Cited by 3,033 publications

References 24 publications

Human obesity as a heritable disorder of the central control of energy balance

Human obesity as a heritable disorder of the central control of energy balance

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

Nutrition-induced differences in body composition, compensatory growth and endocrine status in growing pigs ,

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