Plasma insulin rise precedes rise in<i>ob</i> mRNA expression  and plasma leptin in gold thioglucose-obese mice

Bryson, Janet M.; Phuyal, Jenny L.; Proctor, Deborah R.; Blair, S.C.; Caterson, Ian D.; Cooney, Gregory J.

doi:10.1152/ajpendo.1999.276.2.e358

Cited by 25 publications

(28 citation statements)

References 23 publications

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“…Insulin has previously been shown to be important in the leptin response to nutritional stimuli, with both sustained hyperinsulinaemia being associated with increased serum leptin levels, and the fall in serum leptin with fasting being attributed to the fall in serum insulin. 2,3,7 Insulin also regulated leptin levels during hyperinsulinaemic clamps in both humans and rodents, with an increased leptin response produced from a greater dose of insulin. 22,23 Glucose has also been postulated as a signal of nutritional status.…”

Section: Discussionmentioning

confidence: 99%

“…However, leptin levels can be increased or decreased acutely, independently of changes in adiposity. [1][2][3] Fasting causes a significant reduction in serum leptin and leptin gene expression. [2][3][4][5][6][7][8] The fasting-induced reduction in leptin gene expression can be reversed by refeeding or the administration of insulin or glucose.…”

Section: Introductionmentioning

confidence: 99%

“…[1][2][3] Fasting causes a significant reduction in serum leptin and leptin gene expression. [2][3][4][5][6][7][8] The fasting-induced reduction in leptin gene expression can be reversed by refeeding or the administration of insulin or glucose. 4,5,9 In vitro, leptin secretion is stimulated acutely by both glucose [10][11][12] and insulin [13][14][15][16] and inhibited by nonesterified fatty acids (NEFA).…”

Section: Introductionmentioning

confidence: 99%

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Insulin determines leptin responses during a glucose challenge in fed and fasted rats

et al. 2005

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OBJECTIVE: Leptin secretion has been shown to respond acutely to changes in blood glucose and insulin. Nutritional state also has a marked effect on both the level of circulating leptin protein and leptin gene expression. The aim of this study was to assess whether the prior nutritional state altered the leptin secretory response to an acute glucose challenge, and to determine potential mechanisms. DESIGN: Male fed or fasted rats (200-250 g) were administered a single intravenous glucose bolus (1, 4 or 7 g/kg). The serum leptin, glucose, insulin and free fatty acid responses were studied over the following 5 h. The level of leptin gene expression and leptin protein was then determined in the epididymal fat pads, and in fed and fasted untreated rats for basal comparison. RESULTS: Leptin secretion in response to glucose was suppressed in fasted rats following all glucose doses. The total leptin response was correlated with the total insulin response in all conditions (r ¼ 0.85) and with the glucose response in fed rats (r ¼ 0.69). Both leptin gene expression and leptin protein content were lower in basal fasted rats. Leptin gene expression and leptin protein content still remained lower 5 h following a glucose bolus but there was partial reversal of the effects of fasting following the 7 g/kg glucose dose. CONCLUSIONS: Leptin secretion in response to an intravenous glucose bolus was determined by the insulin response and was significantly suppressed in fasted compared to fed rats. In addition to differences in the total insulin response of the animals, lower leptin responses may be facilitated by lower levels of both leptin gene mRNA and pre-existing leptin protein in epididymal adipose tissue of fasted rats.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

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Insulin determines leptin responses during a glucose challenge in fed and fasted rats

et al. 2005

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“…These data suggest that the effects of the POMC transgene on glucose homeostasis may be at least partially independent of effects on energy homeostasis. This conclusion is consistent with several observations: 1) central administration of MTII results in decreased basal insulin secretion within 1 h after injection in both leptin-deficient and wild-type mice (26); 2) young mice with a disrupted Mc4r gene exhibit elevated plasma insulin levels before the onset of hyperphagia and abnormal weight gain (26); 3) in goldthioglucose (GTG)-treated mice, another animal model of obesity and type 2 diabetes associated with reduced hypothalamic POMC (10), hyperinsulinemia is also evident within 1 week after GTG treatment preceding the progressive increase in adiposity (40); and 4) insulin resistance is …”

Section: Discussionmentioning

confidence: 99%

Transgenic Neuronal Expression of Proopiomelanocortin Attenuates Hyperphagic Response to Fasting and Reverses Metabolic Impairments in Leptin-Deficient Obese Mice

et al. 2003

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Hypothalamic proopiomelanocortin (POMC) gene expression is reduced in many forms of obesity and diabetes, particularly in those attributable to deficiencies in leptin or its receptor. To assess the functional significance of POMC in mediating metabolic phenotypes associated with leptin deficiency, leptin-deficient mice bearing a transgene expressing the POMC gene under control of the neuron-specific enolase promoter were produced. The POMC transgene attenuated fastinginduced hyperphagia in wild-type mice. Furthermore, the POMC transgene partially reversed obesity, hyperphagia, and hypothermia and effectively normalized hyperglycemia, glucosuria, glucose intolerance, and insulin resistance in leptin-deficient mice. Effects of the POMC transgene on glucose homeostasis were independent of the partial correction of hyperphagia and obesity. Furthermore, the POMC transgene normalized the profile of hepatic and adipose gene expression associated with gluconeogenesis, glucose output, and insulin sensitivity. These results indicate that central POMC is a key modulator of glucose homeostasis and that agonists of POMC products may provide effective therapy in treating impairments in glucose homeostasis when hypothalamic POMC expression is reduced, as occurs with leptin deficiency, hypothalamic damage, and aging. Diabetes 52:2675-2683, 2003 M any forms of obesity and diabetes are associated with impairments in the production of (1-5), processing of (6,7), or sensitivity to (8,9) products of the proopiomelanocortin (Pomc) gene. In particular, ablation of leptin or its receptor causes reduced hypothalamic expression of POMC as well as obesity and impairments in glucose metabolism (1-3). Fasting also leads to reduced leptin and reduced expression of hypothalamic POMC (3). Similarly, hypothalamic POMC expression is reduced in other conditions involving impairments in glucose metabolism caused by hypothalamic lesions (10), mutations in the tubby and nhlh2 genes (11,12), aging (13), or insulin deficiency (14). The suggestion that reduced POMC may actually be a cause of the metabolic impairments comes from the observation that mutations in the Pomc gene lead to metabolic impairments in humans (4) and mice (5).It is plausible that the POMC-derived peptide ␣-melanocyte-stimulating hormone (MSH) mediates many of the effects of hypothalamic POMC on metabolic function, as central injection of ␣-MSH or an ␣-MSH agonist decreases food intake and increases energy expenditure (8,15,16), whereas central injection of a melanocortin receptor antagonist increases food intake and decreases energy expenditure (17-19). Because the blockade of ␣-MSH signaling blocks the acute effects of leptin on feeding behavior (20), ␣-MSH may mediate some of leptin's metabolic effects and therefore reduced hypothalamic POMC may mediate effects of leptin deficiency on metabolic and neuroendocrine impairments. Accumulating genetic data also support a role for the melanocortin system in the regulation of glucose metabolism. Agouti mice develop obesity, hyperphagia...

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“…Over a range of physiological conditions from fasting (low) to hyperinsulinaemia, serum insulin correlated with leptin levels. [1][2][3][4][5] Insulin may regulate leptin secretion by a number of potential mechanisms either directly or by intermediates of insulin signalling pathways acting on leptin gene (ob) transcription. [6][7][8] It may also increase leptin production directly, either via a global increase in translation rate 6 or a specific increase in the rate of translation of ob mRNA.…”

Section: Introductionmentioning

confidence: 99%

Leptin secretion is related to glucose-derived lipogenesis in isolated adipocytes

et al. 2006

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Objective: Leptin secretion in rats is regulated acutely by nutritional state. Insulin plays an important role in this acute nutritional regulation both directly and indirectly through effects on glucose metabolism. The aim of this study was to investigate if the fasting-induced suppression of leptin secretion was reversed by incubation under conditions mimicking nutritional repletion. Design: Leptin secretion and glucose metabolism were measured following incubation with glucose and insulin in adipocytes isolated from fed and fasted rats. Results: Leptin secretion was stimulated by incubation with glucose and insulin in adipocytes isolated from fed but not from fasted rats as was glucose flux through oxidative and lipogenic pathways. Ob expression and intracellular leptin content were decreased in adipocytes isolated from fasted rats throughout the whole incubation period. Suppression of glucose metabolism with cytochalasin B was accompanied by suppression of leptin secretion. The amount of leptin secretion correlated with the glucose incorporated into lipid under insulin-stimulated conditions. Conclusions: It is proposed that glucose incorporation into lipid, at least during insulin-stimulated conditions, reflects the metabolic status of the adipocyte and may be a more important regulator of leptin production and secretion than circulating glucose or insulin levels.

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Plasma insulin rise precedes rise inob mRNA expression and plasma leptin in gold thioglucose-obese mice

Cited by 25 publications

References 23 publications

Insulin determines leptin responses during a glucose challenge in fed and fasted rats

Insulin determines leptin responses during a glucose challenge in fed and fasted rats

Transgenic Neuronal Expression of Proopiomelanocortin Attenuates Hyperphagic Response to Fasting and Reverses Metabolic Impairments in Leptin-Deficient Obese Mice

Leptin secretion is related to glucose-derived lipogenesis in isolated adipocytes

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