20 YEARS OF LEPTIN: Leptin at 20: an overview

Friedman, Jeffrey M.

doi:10.1530/joe-14-0405

Cited by 209 publications

(159 citation statements)

References 65 publications

Supporting

Mentioning

149

Contrasting

Unclassified

Order By: Relevance

“…The human leptin gene LEP, also known as the ob gene, encodes a protein that is 16 kDa in weight and 167 amino acids long [15]. It was isolated in 1994 by Jeffrey Friedman [15] and has since been dubbed "the hunger gene" because of its primary action to regulate food intake and energy expenditure.…”

Section: Leptinmentioning

confidence: 99%

“…It was isolated in 1994 by Jeffrey Friedman [15] and has since been dubbed "the hunger gene" because of its primary action to regulate food intake and energy expenditure. The peptide hormone is secreted from adipose tissue in proportion to an individual's fat mass and exerts its effects via blood circulation with targets such as the central nervous system, muscle, liver and adipose tissue [16].…”

Section: Leptinmentioning

confidence: 99%

See 1 more Smart Citation

Adipose tissue, obesity and adipokines: role in cancer promotion

Booth

Magnuson

Fouts

et al. 2015

Hormone Molecular Biology and Clinical Investigation

250

235

View full text Add to dashboard Cite

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.

show abstract

Section: Leptinmentioning

confidence: 99%

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

250

235

View full text Add to dashboard Cite

show abstract

“…3 A and B). It is well known that both genetic-and diet-induced obesity account for increasing leptin levels and elicit leptin resistance in a tissuespecific manner (41). Immunoblotting experiments were performed on the leptin receptor, ObR, in hypothalamic lysates (Fig.…”

Section: Snap-25b Deficiency Impairs Insulin Secretion and Glucose Homentioning

confidence: 99%

“…Obesity and its associated metabolic disorders are characterized by changes in the release of humoral factors such as leptin and ghrelin (41). We analyzed basal serum leptin and ghrelin levels after diet intervention ( Fig.…”

Section: (E and F) Hypothalamic Pstat3 Is Decreased In All Experimentmentioning

confidence: 99%

Replacing SNAP-25b with SNAP-25a expression results in metabolic disease

Valladolid‐Acebes

Daraio

Brismar

et al. 2015

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

Synaptosomal-associated protein of 25 kDa (SNAP-25) is a key molecule in the soluble N-ethylmaleimide-sensitive factor attachment protein (SNARE) complex mediating fast Ca 2+ -triggered release of hormones and neurotransmitters, and both splice variants, SNAP-25a and SNAP-25b, can participate in this process. Here we explore the hypothesis that minor alterations in the machinery mediating regulated membrane fusion can increase the susceptibility for metabolic disease and precede obesity and type 2 diabetes. Thus, we used a mouse mutant engineered to express normal levels of SNAP-25 but only SNAP-25a. These SNAP-25b-deficient mice were exposed to either a control or a high-fat/high-sucrose diet. Monitoring of food intake, body weight, hypothalamic function, and lipid and glucose homeostases showed that SNAP-25b-deficient mice fed with control diet developed hyperglycemia, liver steatosis, and adipocyte hypertrophy, conditions dramatically exacerbated when combined with the high-fat/high-sucrose diet. Thus, modified SNARE function regulating stimulus-dependent exocytosis can increase the vulnerability to and even provoke metabolic disease. When combined with a high-fat/high-sucrose diet, this vulnerability resulted in diabesity. Our SNAP-25b-deficient mouse may represent a diabesity model.O n-going lifestyle changes, including oversized meals with excessive amounts of sugar and fat, have led to a worldwide pandemic of obesity and type 2 diabetes (T2D) (1). These diseases and their comorbidities cause individual suffering and represent a heavy financial burden on society (2, 3). The term "diabesity" is used to define the coincidence of obesity with T2D under conditions of exaggerated intake of energy-dense diets (4-6). Moreover, genomewide association studies (GWAS) have identified polymorphisms associated with obesity and T2D, indicating that genetic factors predispose certain individuals to diabesity (7-11).Signs of metabolic diseases include impaired regulated release of hormones, particularly insulin as in T2D (4, 12). Likewise, the secretion of inflammatory markers and other peripheral bioactive peptides is either increased (e.g., leptin, resistin, and adipsin) or decreased (e.g., ghrelin and adiponectin) (13-16). Synaptic and nonsynaptic transmission involving the release of neuropeptides and neurotransmitters, especially in hypothalamic areas controlling eating behavior and energy balance, are involved too (17)(18)(19).In excitable cells, the release of messenger molecules is a consequence of regulated membrane fusion and involves soluble N-ethylmaleimide-sensitive factor attachment proteins (SNAREs) (20, 21), including synaptosomal-associated protein of 25 kDa (SNAP-25). SNAP-25 is expressed as two developmentally regulated and alternatively spliced isoforms, SNAP-25a and SNAP-25b, which differ in only 9 of 206 amino acids (22, 23). In the mouse brain, SNAP-25a precedes SNAP-25b expression during development, but by the second postnatal week SNAP-25b becomes the major splice variant, concomitantly with a dr...

show abstract

“…2). (Friedman 2014, Park & Ahima 2015. Leptin receptors are highly expressed in the hypothalamus where they are required for the regulation of appetite, energy expenditure, body weight, thermogenesis, fertility and immune function (Ahima et al 1996, Wada et al 2014, Freitas Lima et al 2015, Park et al 2015.…”

Section: Adipocyte-derived Factorsmentioning

confidence: 99%

Adipocytes, aldosterone and obesity-related hypertension

Cat¹,

Friederich‐Persson²,

White³

et al. 2016

Journal of Molecular Endocrinology

View full text Add to dashboard Cite

Aldosterone and obesity a nguyen dinh cat and others 57:1 F7-F21 AbstractUnderstanding the mechanisms linking obesity with hypertension is important in the current obesity epidemic as it may improve therapeutic interventions. Plasma aldosterone levels are positively correlated with body mass index and weight loss in obese patients is reported to be accompanied by decreased aldosterone levels. This suggests a relationship between adipose tissue and the production/secretion of aldosterone. Aldosterone is synthesized principally by the adrenal glands, but its production may be regulated by many factors, including factors secreted by adipocytes. In addition, studies have reported local synthesis of aldosterone in extra-adrenal tissues, including adipose tissue. Experimental studies have highlighted a role for adipocyte-secreted aldosterone in the pathogenesis of obesity-related cardiovascular complications via the mineralocorticoid receptor. This review focuses on how aldosterone secretion may be influenced by adipose tissue and the importance of these mechanisms in the context of obesity-related hypertension.

show abstract

20 YEARS OF LEPTIN: Leptin at 20: an overview

Cited by 209 publications

References 65 publications

Adipose tissue, obesity and adipokines: role in cancer promotion

Adipose tissue, obesity and adipokines: role in cancer promotion

Replacing SNAP-25b with SNAP-25a expression results in metabolic disease

Adipocytes, aldosterone and obesity-related hypertension

Contact Info

Product

Resources

About