Lipid deposition in rats centrally infused with leptin in the presence or absence of corticosterone

Arvaniti, Konstantinia; Richard, Denis; Picard, Frédéric; Deshaies, Yves

doi:10.1152/ajpendo.2001.281.4.e809

Cited by 12 publications

(7 citation statements)

References 59 publications

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“…This could be explained by the lower lipogenic capacity of eWAT compared with the liver. In addition, the decreased expression of PECK-C in eWAT, an enzyme involved in glyceroneogenesis, and the significant reduction in lipoprotein lipase activity reported in eWAT after central leptin administration (12) could reduce the incorporation of exogenous FA to TAG in this tissue, and then contribute to explaining the unaltered TAG-FA composition of the eWAT after the central leptin treatment. Furthermore, central leptin administration impairs the insulin-stimulated glucose uptake in eWAT (27) (unpublished observations), which would also contribute to reducing the glycerol availability and, thus, de novo TAG synthesis in this tissue.…”

Section: Discussionmentioning

confidence: 99%

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Tissue-Specific Effects of Central Leptin on the Expression of Genes Involved in Lipid Metabolism in Liver and White Adipose Tissue

et al. 2007

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L EPTIN, A CYTOKINE produced mainly by the white adipose tissue (WAT), is actively involved in the control of body weight and food intake. Dysregulations of leptin actions are associated with obesity, insulin resistance, and type 2 diabetes. These facts point to leptin and its actions as targets of study to clarify these metabolic disorders and identify potential therapeutic strategies. Several reports have shown that leptin regulates energy homeostasis by controlling peripheral lipid metabolism, and leptin administration reduces triacylglyceride (TAG) stores and promotes fatty acid (FA) oxidation in lean and adipose tissues (1-7). Therefore, it has been postulated that one of the roles of leptin is to reduce lipid accumulation in nonadipose tissues, preventing lipotoxicity (8).In the liver an acute iv leptin infusion decreases liver TAG secretion, increases hepatic FA oxidation and ketogenesis, and, as a result, decreases liver TAG levels (9). However, an acute intracerebroventricular (icv) leptin administration does not decrease liver TAG levels (9 -11). On the other hand, chronic icv leptin treatment decreases TAG content in liver and plasma compared with ad libitum fed controls (12), suggesting that leptin, acting at central level, plays an important role depleting TAG levels in this tissue.In WAT, the effect of leptin on lipid metabolism has not been fully characterized and remains controversial. Thus, adenovirus-induced hyperleptinemia increases the expression of enzymes of FA oxidation such as acyl-coenzyme A oxidase and carnitine palmitoyl transferase (CPT)-1, and depletes the TAG without a concomitant increase in the levels of circulating free FAs (3). This suggests that leptin favored intracellular FA oxidation in adipocytes. Furthermore, treatment of isolated rat adipocytes with leptin up-regulates the expression of acyl-coenzyme A oxidase, CPT-1, uncoupling protein 2, and peroxisome proliferator activated receptor (PPAR) ␣, all of which are involved in lipid oxidation (13). In addition, in vivo (14) and in vitro (15) studies indicated a paracrine/autocrine stimulation of lipolysis in rodent adi-

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Section: Discussionmentioning

confidence: 99%

“…However, an acute intracerebroventricular (icv) leptin administration does not decrease liver TAG levels (9 -11). On the other hand, chronic icv leptin treatment decreases TAG content in liver and plasma compared with ad libitum fed controls (12), suggesting that leptin, acting at central level, plays an important role depleting TAG levels in this tissue.…”

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confidence: 93%

Tissue-Specific Effects of Central Leptin on the Expression of Genes Involved in Lipid Metabolism in Liver and White Adipose Tissue

et al. 2007

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“…The observation that the weight-reducing effects of ADX are especially potent in animals that lack a leptin signal, however, suggests that GCs regulate energy homeostasis via a mechanism that is, at least partly, leptin independent. Together, these observations raise the possibility that the opposing effects of GCs and leptin in energy homeostasis (1,30) involve the reciprocal regulation of a common downstream central nervous system (CNS) pathway.…”

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confidence: 99%

Physiological regulation of hypothalamic IL-1β gene expression by leptin and glucocorticoids: implications for energy homeostasis

Wisse¹,

Ogimoto²,

Morton³

et al. 2004

American Journal of Physiology-Endocrinology and Metabolism

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2004.-Interleukin-1␤ (IL-1␤) is synthesized in a variety of tissues, including the hypothalamus, where it is implicated in the control of food intake. The current studies were undertaken to investigate whether hypothalamic IL-1␤ gene expression is subject to physiological regulation by leptin and glucocorticoids (GCs), key hormones involved in energy homeostasis. Adrenalectomy (ADX) increased hypothalamic IL-1␤ mRNA levels twofold, measured by real-time PCR (P Ͻ 0.05 vs. sham-operated controls), and this effect was blocked by subcutaneous infusion of a physiological dose of corticosterone. Conversely, hypothalamic IL-1␤ mRNA levels were reduced by 30% in fa/fa (Zucker) rats, a model of genetic obesity caused by leptin receptor mutation (P ϭ 0.01 vs. lean littermates), and the effect of ADX to increase hypothalamic IL-1␤ mRNA levels in fa/fa rats (P ϭ 0.02) is similar to that seen in normal animals. Moreover, fasting for 48 h (which lowers leptin and raises corticosterone levels) reduced hypothalamic IL-1␤ mRNA levels by 30% (P ϭ 0.02), and this decrease was fully reversed by refeeding for 12 h. Thus leptin and GCs exert opposing effects on hypothalamic IL-1␤ gene expression, and corticosterone plays a physiological role to limit expression of this cytokine in both the presence and absence of intact leptin signaling. Consistent with this hypothesis, systemic leptin administration to normal rats (2 mg/kg ip) increased hypothalamic IL-1␤ mRNA levels twofold (P Ͻ 0.05 vs. vehicle), an effect similar to that of ADX. These data support a model in which expression of hypothalamic IL-1␤ is subject to opposing physiological regulation by corticosterone and leptin.interleukin-1␤; cytokine; corticosterone; food intake; appetite; obesity; anorexia THE CLINICAL FINDINGS OF ANOREXIA and weight loss in patients with adrenal insufficiency and of increased appetite and weight gain in conditions of glucocorticoid (GC) excess have long suggested a role for the adrenal gland in energy homeostasis. Moreover, most rodent models of obesity are dependent on the action of GCs, since they are prevented or reversed by adrenalectomy (ADX) (29). Furthermore, anorexia induced by the adipocyte hormone leptin is augmented by ADX via a mechanism that is blocked by GC administration (30), suggesting that GCs play a physiological role to antagonize the central actions of leptin. The observation that the weight-reducing effects of ADX are especially potent in animals that lack a leptin signal, however, suggests that GCs regulate energy homeostasis via a mechanism that is, at least partly, leptin independent. Together, these observations raise the possibility that the opposing effects of GCs and leptin in energy homeostasis (1, 30) involve the reciprocal regulation of a common downstream central nervous system (CNS) pathway.Several recent observations identify the proinflammatory cytokine interleukin-1␤ (IL-1␤) as a potential target for the opposing effects of leptin and GCs on hypothalamic systems governing energy balance. Administration of IL-1␤,...

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“…lipid infusion [3], resulting in a decrease in noradrenaline-mediated lipolysis [19]. The decrease in plasma NEFA concentration may also be a consequence of an increase in liver triglyceride storage [20,21], resulting partly from higher plasma corticosterone levels. The fact that lipid infusion did not alter basal glucose kinetics or insulin action could be due to the rather short duration of the infusion.…”

Section: Discussionmentioning

confidence: 99%

Intracerebroventricular infusion of a triglyceride emulsion leads to both altered insulin secretion and hepatic glucose production in rats

Clément

Cruciani-Guglielmacci

Magnan

et al. 2002

Pfl�gers Archiv European Journal of Physiology

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We investigated here whether non-esterified fatty acids (NEFA) influence insulin secretion and action through a direct effect on central nervous system sites involved in the control of glucose homeostasis. Normal Wistar rats received a 48-h intracerebroventricular infusion of either a 10% triglyceride (Intralipid, IL)/heparin emulsion (IL/h) or saline/heparin solution (control). At 48 h, insulin secretion as measured by an intravenous glucose tolerance test, was more elevated in IL/h than in control rats. Pancreatic noradrenaline turnover was decreased by 57% in IL/h rats, suggesting low pancreatic sympathetic output that could account partly for the elevated insulin secretion. The time course of glycaemia was similar in both groups, suggesting insulin resistance. Euglycaemic-hyperinsulinaemic clamps were imposed to assess peripheral and hepatic insulin sensitivity. At each insulin concentration glucose utilization was increased to a similar extent in both groups, whereas hepatic glucose production decreased much less in IL/h than in control rats. Hepatic insulin insensitivity could be related partly to activation of the hypothalamic-pituitary-adrenocortical axis, since plasma corticosterone concentration was significantly increased in IL/h rats compared with controls. Our data indicate that lipids may alter both insulin secretion and hepatic sensitivity to insulin through their effect on central nervous system.

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Lipid deposition in rats centrally infused with leptin in the presence or absence of corticosterone

Cited by 12 publications

References 59 publications

Tissue-Specific Effects of Central Leptin on the Expression of Genes Involved in Lipid Metabolism in Liver and White Adipose Tissue

Tissue-Specific Effects of Central Leptin on the Expression of Genes Involved in Lipid Metabolism in Liver and White Adipose Tissue

Physiological regulation of hypothalamic IL-1β gene expression by leptin and glucocorticoids: implications for energy homeostasis

Intracerebroventricular infusion of a triglyceride emulsion leads to both altered insulin secretion and hepatic glucose production in rats

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