Leptin Signaling and Obesity

Yang, Ronghua; Barouch, Lili A.

doi:10.1161/circresaha.107.156596

Cited by 280 publications

(137 citation statements)

References 192 publications

(217 reference statements)

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“…The up-regulation of leptin mRNA levels is very intriguing and agrees with the results of a previous study (Angle et al 2013). Leptin production by adipocytes is proportional to their fat content; leptin serum levels are higher in obese subjects, and are directly correlated to adipose mass and adipocyte contents (Fried et al 2000, Yang & Barouch 2007. These considerations clearly indicate that BPA treatment may have an obesogenic effect.…”

Section: Discussionsupporting

confidence: 86%

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders

Menale¹,

Piccolo²,

Cirillo³

et al. 2015

Journal of Molecular Endocrinology

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Bisphenol A (BPA) is a xenobiotic endocrine-disrupting chemical. In vitro and in vivo studies have indicated that BPA alters endocrine-metabolic pathways in adipose tissue, which increases the risk of metabolic disorders and obesity. BPA can affect adipose tissue and increase fat cell numbers or sizes by regulating the expression of the genes that are directly involved in metabolic homeostasis and obesity. Several studies performed in animal models have accounted for an obesogen role of BPA, but its effects on human adipocytesespecially in children -have been poorly investigated. The aim of this study is to understand the molecular mechanisms by which environmentally relevant doses of BPA can interfere with the canonical endocrine function that regulates metabolism in mature human adipocytes from prepubertal, non-obese children. BPA can act as an estrogen agonist or antagonist depending on the physiological context. To identify the molecular signatures associated with metabolism, transcriptional modifications of mature adipocytes from prepubertal children exposed to estrogen were evaluated by means of microarray analysis. The analysis of deregulated genes associated with metabolic disorders allowed us to identify a small group of genes that are expressed in an opposite manner from that of adipocytes treated with BPA. In particular, we found that BPA increases the expression of pro-inflammatory cytokines and the expression of FABP4 and CD36, two genes involved in lipid metabolism. In addition, BPA decreases the expression of PCSK1, a gene involved in insulin production. These results indicate that exposure to BPA may be an important risk factor for developing metabolic disorders that are involved in childhood metabolism dysregulation.

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Section: Discussionsupporting

confidence: 86%

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders

Menale¹,

Piccolo²,

Cirillo³

et al. 2015

Journal of Molecular Endocrinology

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“…It is also proposed that obesity causes a reduction in blood-brain barrier transport, which reduces accessibility of leptin to the hypothalamus [21]. Overall, leptin resistance leads to dysregulated cytokine signaling, reduced appetite suppression and energy expenditure, which perpetuates inflammation and subsequently further increases adiposity and its associated co-morbidities [22].…”

Section: Leptinmentioning

confidence: 99%

Adipose tissue, obesity and adipokines: role in cancer promotion

Booth

Magnuson

Fouts

et al. 2015

Hormone Molecular Biology and Clinical Investigation

212

222

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Adipose tissue is a complex organ with endocrine, metabolic and immune regulatory roles. Adipose depots have been characterized to release several adipocytokines that work locally in an autocrine and paracrine fashion or peripherally in an endocrine fashion. Adipocyte hypertrophy and excessive adipose tissue accumulation, as occurs during obesity, dysregulates the microenvironment within adipose depots and systemically alters peripheral tissue metabolism. The term "adiposopathy" is used to describe this promotion of pathogenic adipocytes and associated adipose -elated disorders. Numerous epidemiological studies confirm an association between obesity and various cancer forms. Proposed mechanisms that link obesity/adiposity to high cancer risk and mortality include, but are not limited to, obesity-related insulin resistance, hyperinsulinemia, sustained hyperglycemia, glucose intolerance, oxidative stress, inflammation and/or adipocktokine production. Several epidemiological studies have demonstrated a relationship between specific circulating adipocytokines and cancer risk. The aim of this review is to define the function, in normal weight and obesity states, of wellcharacterized and novel adipokines including leptin, adiponectin, apelin, visfatin, resistin, chemerin, omentin, nesfatin and vaspin and summarize the data that relates their dysfunction, whether associated or direct effects, to specific cancer outcomes. Overall research suggests most adipokines promote cancer cell progression via enhancement of cell proliferation and migration, inflammation and anti-apoptosis pathways, which subsequently can prompt cancer metastasis. Further research and longitudinal studies are needed to define the specific independent and additive roles of adipokines in cancer progression and reoccurrence.

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“…LRb is a cytokine receptor that activates Jak2 (Janus tyrosine kinase 2) (21,22). Jak2 then associates with specific C-terminal domains of the LR, resulting in transphosphorylation of Jak2 and phosphorylation of specific Tyr residues located within the C-terminal domain of LRb (Fig.…”

Section: Possible Molecular Mechanisms Of the Differential Effects Ofmentioning

confidence: 99%

Obesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins

Hall

Silva

Carmo

et al. 2010

Journal of Biological Chemistry

421

397

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Excess weight gain contributes to increased blood pressure in most patients with essential hypertension. Although the mechanisms of obesity hypertension are not fully understood, increased renal sodium reabsorption and impaired pressure natriuresis play key roles. Several mechanisms contribute to altered kidney function and hypertension in obesity, including activation of the sympathetic nervous system, which appears to be mediated in part by increased levels of the adipocyte-derived hormone leptin, stimulation of pro-opiomelanocortin neurons, and subsequent activation of central nervous system melanocortin 4 receptors.The worldwide prevalence of obesity and associated cardiometabolic diseases have increased dramatically in the past 2-3 decades, rapidly becoming major challenges to the health care systems of most industrialized countries. Current estimates indicate that Ͼ1 billion people in the world are overweight or obese (1). In the United States, at least 65% of adults are overweight, and approximately one-third of adults are obese with a body mass index (defined as kilograms of weight/m 2 of height) of Ͼ30 (2). In children, the prevalence of obesity has also risen rapidly in parallel with increasing obesity in adults; a recent report indicates that 18.4% of 4-year-old children in the United States are obese, with significantly higher rates of obesity in Hispanic, black, and Native American children (3).Associated with obesity is a cascade of metabolic and cardiovascular disorders, including hypertension, a primary mediator of obesity-induced cardiovascular disease. Population studies show that excess weight gain predicts future development of hypertension, and the relationship between body mass index and blood pressure (BP) 2 appears to be nearly linear in diverse populations throughout the world (4). Some studies suggest that excess weight gain may account for 65-75% of human essential hypertension (5). Moreover, clinical studies indicate that weight loss is effective in primary prevention of hypertension and in reducing BP in most hypertensive subjects (6).Although the importance of obesity as a major cause of essential hypertension is well established, the physiological and molecular mechanisms that mediate the BP effects of excess weight gain are only beginning to be elucidated. Excess Weight Gain Increases Renal SodiumReabsorption and Impairs Pressure Natriuresis Table 1 summarizes some of the changes in cardiovascular, neurohormonal, and renal function that occur in obese humans and experimental animals (4,7,8). Notable changes, in addition to increased BP, include increases in cardiac output and heart rate as well as activation of the sympathetic nervous system (SNS) and renin-angiotensin-aldosterone system (RAAS). Rapid weight gain also stimulates renal tubular sodium reabsorption, and obese subjects require higher than normal BP to maintain balance between intake and renal excretion of sodium, indicating impaired renal pressure natriuresis (4).Three factors are especially important in increasing re...

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Leptin Signaling and Obesity

Cited by 280 publications

References 192 publications

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders

Bisphenol A effects on gene expression in adipocytes from children: association with metabolic disorders

Adipose tissue, obesity and adipokines: role in cancer promotion

Obesity-induced Hypertension: Role of Sympathetic Nervous System, Leptin, and Melanocortins

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