Modulation of Direct Leptin Signaling by Soluble Leptin Receptor

Yang, Guoqing; Ge, Hongfei; Boucher, Anne; Yu, Xinxin; Li, Cai

doi:10.1210/me.2004-0027

Cited by 115 publications

(89 citation statements)

References 51 publications

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“…1). In human plasma as well as in vitro models, SLR sequesters leptin, preventing the activation of ObR signaling (Ge et al, 2002;Yang et al, 2004). The abundance of SLR is regulated by different physiological and pathological conditions, thus this receptor may serve as a potent modulator of leptin action in various tissues (Chan et al, 2002).…”

Section: Leptin Signalingmentioning

confidence: 99%

Leptin and cancer

Garofalo

Surmacz

2005

Journal Cellular Physiology

543

496

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The prevalence of obesity has markedly increased over the past two decades, especially in the industrialized countries. While the impact of excess body weight on the development of cardiac disease and diabetes has been well documented, the link between obesity and carcinogenesis is just being recognized. This review will focus on the link between leptin, a cytokine that is elevated in obese individuals, and cancer development. First, we briefly discuss the biological functions of leptin and its signaling pathways. Then, we summarize the effects of leptin on different cancer types in experimental cellular and animal models. Next, we analyze epidemiological data on the relationship between obesity and the presence of cancer or cancer risk in patients. Finally, leptin as a target for cancer treatment and prevention will be discussed.

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Section: Leptin Signalingmentioning

confidence: 99%

Leptin and cancer

Garofalo

Surmacz

2005

Journal Cellular Physiology

543

496

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“…At least three potential circulating blockers of leptin action have been reported. Two of these, the soluble leptin receptor and C-reactive protein, have already been shown to be increased in the circulation of fa/fa ZDF rats (26,27) and to impair the action of leptin (27,28).…”

Section: Fat Pads From ϩ/ϩ Donors Do Not Respond To Hyperleptinemia Wmentioning

confidence: 99%

“…Hypertriglyceridemia, one of the circulating factors proposed to block the hypothalamic action of leptin (29), was excluded as the cause of the unresponsiveness of the ϩ/ϩ fat pads to hyperleptinemia when they had been transplanted into fa/fa recipients. However, soluble Lepr remains a highly likely candidate as a circulating blocker in fa/fa rats because it is increased in the ZDF fa/fa rats (26) and is known to impair leptin action (28). More recently, elevated C-reactive protein levels of obesity have been reported to attenuate leptin action (27).…”

Section: Tablementioning

confidence: 99%

Combined Leptin Actions on Adipose Tissue and Hypothalamus Are Required to Deplete Adipocyte Fat in Lean Rats

Park

Wang

Lee

et al. 2006

Journal of Biological Chemistry

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Intense hyperleptinemia completely depletes adipocyte fat of normal rats within 14 days. To determine the mechanism, epididymal fat pads from normal wild-type (؉/؉) and obese (fa/fa) Zucker Diabetic Fatty (ZDF) donor rats were transplanted into normal ؉/؉ and fa/fa ZDF recipients. Hyperleptinemia induced by adenovirus-leptin administration depleted all fat from native fat pads and from fat transplants from ؉/؉ donors but not from transplants from ZDF fa/fa donors with defective leptin receptors. In both native and transplanted ؉/؉ fat pads, large numbers of mitochondria were apparent, and genes involved in fatty acid oxidation were up-regulated. However, ؉/؉ fat pads transplanted into fa/fa recipients did not respond to hyperleptinemia, suggesting lack of an essential leptin-stimulated cohormone(s). In ؉/؉ but not in fa/fa rats, plasma catecholamine levels rose, and both P-STAT3 and P-CREB increased in adipose tissue, suggesting that both direct and indirect (hypothalamic) leptin receptor-mediated actions of hyperleptinemia are involved in depletion of adipocyte fat.In normal lean rodents, the induction of hyperleptinemia by administration of recombinant adenovirus containing the leptin cDNA (AdCMV-leptin) causes all visible fat to melt away within 7 days (1). In what is probably the most striking effect of this hormone, white adipocytes are transformed into fatless cells filled with small mitochondria (2). In addition, genes such as ucp-1 (uncoupling protein-1) and pgc-1␣ (peroxisome proliferator-activated receptor-␥-coactivator-1-␣), normally expressed in brown but not white adipocytes, are expressed at high levels, whereas adipocyte markers, such as leptin and aP2, are profoundly down-regulated (2). Despite their similarities to brown adipocytes, these transformed white adipocytes differ sufficiently to warrant designation as a novel derivative cell, the "post-adipocyte" (2). Although fat depletion of adipocytes by hyperleptinemia occurs only in lean and not in obese rodents, understanding of its mechanisms may have implications for the treatment of obesity.The fat depletion induced by experimental hyperleptinemia differs from that of naturally occurring catabolic states, such as starvation and insulin deficiency, in which free fatty acids are released from the adipocytes and oxidized in the liver. The fat depletion of experimental hyperleptinemia is unaccompanied by an increase in plasma free fatty acids or ketones (3, 4), and the molecular and morphologic changes (2) imply that the oxidation takes place within the transformed adipocytes.The pathway by which hyperleptinemia induces transformation of adipocytes to post-adipocytes has not been clearly identified. We know that leptin-responsive centers in the hypothalamus regulate energy metabolism and feeding behavior (3-8), but there is also evidence for direct leptin action on adipocytes (9 -11) and on other tissues (12-17). Here we report that the fat-depleting action of hyperleptinemia requires both direct leptin receptor (Lepr) 3 -mediated action on adi...

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“…In addition, the biologic role of the circulating leptin receptor/binding protein has not as yet been elucidated. [28][29][30][31][32][33] However, many new peripheral actions of leptin have been discovered, underlining that leptin also plays a role in modulating metabolism, energy expenditure, and pathologic processes in humans.…”

Section: Leptinmentioning

confidence: 99%

Obesity in Childhood and Adolescence: a review in the interface between adipocyte physiology and clinical challenges

Körner¹,

Blüher²,

Kapellen³

et al. 2005

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Body weight is regulated by a feedback loop in which peripheral signals report nutritional information to an integratory center in the brain. The cloning of the ob gene is consistent with this concept and suggests that body fat content in adult rodents is regulated by a negative feedback loop centered in the hypothalamus. In recent years a number of additional signaling molecules secreted by adipose tissue have been discovered. These hormones, named adipocytokines, include resistin, adiponectin and visfatin. Among the adipocytokines, adiponectin is perhaps the most interesting compound for the clinician since low adiponectin serum levels have been found in obese subjects and in particular insulin resistant patients. The definition and diagnosis of obesity in children and adolescents are surprisingly difficult. The level of fatness at which morbidity increases is determined on an acturial basis. In children and adolescents the degree of body fat mass depends upon ethnic background, gender, developmental stage and age. Treatment and prevention of obesity in childhood and adolescence are major challenges for todays health care providers and societies. OBESITY DEFINITION IN CHILDRENDirect measurements of body fat content e.g., hydrodensitometry, bioimpedance, or DEXA are useful tools only in scientific studies. Body-mass index (BMI) (weight in kilograms divided by the square of the height in meters) is easy to calculate and is correlated sufficiently with direct measures of fatness. BMI is therefore frequently used to define obesity clinically. A child with a BMI above the 97th centile in regard to age and gender is considered to be obese. A child with a BMI greater than the 90th but below the 97th centile would be considered to be overweight. In adults, a BMI greater than 28 kg/m 2 is associated with an increased risk of morbidity such as stroke, ischemic heart disease, or type II diabetes mellitus. Adults with a BMI greater

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Modulation of Direct Leptin Signaling by Soluble Leptin Receptor

Cited by 115 publications

References 51 publications

Leptin and cancer

Leptin and cancer

Combined Leptin Actions on Adipose Tissue and Hypothalamus Are Required to Deplete Adipocyte Fat in Lean Rats

Obesity in Childhood and Adolescence: a review in the interface between adipocyte physiology and clinical challenges

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