Leptin resistance in obesity: An epigenetic landscape

Crujeiras, Ana B.; Carreira, Marcos C.; Cabia, Begoña; Andrade, Sara; Amil, María; Casanueva, Felipe F.

doi:10.1016/j.lfs.2015.05.003

Cited by 201 publications

(134 citation statements)

References 92 publications

(105 reference statements)

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“…Leptin is an adipocyte-secreted hormone that inhibits food intake and stimulates energy expenditure; however, most obese individuals have hyperleptinaemia and they demonstrate leptin resistance 123 . Hyperleptinaemia is associated with subclinical inflammation in obese subjects and leptin enhances the secretion of IL18 from human monocytes via activation of caspase-1 inflammasomes 124 .…”

Section: [H3] Effect Of Adipokines On Nlrp3 Inflammasomesmentioning

confidence: 99%

Innate immunity in diabetes and diabetic nephropathy

2015

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Abstract:The innate immune system consists of several classes of pattern recognition receptors (PRRs), including membrane-bound Toll-like receptors (TLRs) and nucleotide-binding domain leucine-rich oligomerization domain (NOD)-like receptors (NLRs).These receptors detect pathogen-associated molecular patterns (PAMPs) and danger-associated molecular patterns (DAMPs) in the extracellular and intracellular space. Intracellular NLRs constitute inflammasomes, which activate and release caspase-1, IL1β, and IL18 and thus initiate an inflammatory response. Systemic and local low-grade inflammation and release of proinflammatory cytokines are implicated in the development and progression of diabetes mellitus and diabetic nephropathy. TLR2, TLR4, and the NLRP3 inflammasome are critically involved in the inflammatory responses in pancreatic islets, adipose, liver and kidney tissues. This Review discusses how innate immune system-driven inflammatory processes can lead to apoptosis, tissue fibrosis, and organ dysfunction to cause insulin resistance, impaired insulin secretion, and renal failure. We propose that careful targeting of TLR2, TLR4, and NLRP3 signalling pathways may be beneficial for the treatment of diabetes mellitus and diabetic nephropathy. 2 Key points The innate immune system consists of several classes of pattern recognition receptors, including TLRs and NLRs, which detect pathogen-associated and danger-associated molecular patterns and initiate an inflammatory response  TLR2 and TLR4 are the predominant toll-like receptors expressed on pancreatic β cells that trigger an inflammatory response in insulitis during type 1 diabetes mellitus  TLR2 and TLR4 signaling, and activation of NLRP3 inflammasomes results in production of various proinflammatory cytokines that can induce insulin resistance in type 2 diabetes mellitus (T2DM) and obesity  Innate immune responses in T2DM and obesity are modulated by the status of the gut microbiota, autophagy, and adipokines  TLR2, TLR4, NOD2, and NLRP3 inflammasome-mediated inflammation are involved in the perpetuation of inflammation in diabetic nephropathy  The activation of TLRs and NLRs stimulates the expression of MCP-1, which is associated with the progression of diabetic nephropathy [H1] IntroductionThe prevalence of diabetes mellitus is estimated to be 8.3%, affecting ~387 million people as of 2014. The number of patients living with diabetes mellitus is expected to increase to ~592 million by 2035, as reported by the International Diabetes Federation 1 . The incidence of end-stage renal disease (ESRD) is also rapidly increasing worldwide but varies up to 15-fold by country. In 2012, the number of new diagnoses of ESRD worldwide ranged from 25 to 467 patients per million. The proportion of new cases of ESRD with diabetes mellitus as the primary cause also differs by country, with 66% cases reported in Singapore and 12-16% cases reported in Ukraine, Romania, and the Netherlands 2 . Although intensified multifactorial intervention in patients with type 2 diabete...

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Section: [H3] Effect Of Adipokines On Nlrp3 Inflammasomesmentioning

confidence: 99%

Innate immunity in diabetes and diabetic nephropathy

2015

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“…The opposite correlation has been seen in obese individuals, where leptin levels are increased and ghrelin levels decreased (32,33). These individuals are considered leptin resistant (47). Obesity has also been associated with reduced adiponectin secretion (48).…”

Section: Arv1mentioning

confidence: 99%

Mice lacking have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

Gallo-Ebert¹,

Francisco²,

Liu³

et al. 2018

Journal of Biological Chemistry

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“…When energy imbalance occurs, excessive calories accumulate as triglycerides in adipose tissue, leading to overweight and obesity. Hence, a better understanding of the energy homeostasis in a human body holds the key to finding the exact causes of obesity (Paspala et al, 2012;Szczesna et al, 2013;Chopra et al, 2014;Pan et al, 2014;Crujeiras et al, 2015;Park & Ahima, 2015;Sáinz et al, 2015).…”

Section: Energy Homeostasis and Leptin Deficiencymentioning

confidence: 99%

“…However, in recent years researchers have demonstrated that a multi-therapy of leptin in combination with other leptin sensitisers may be able to improve peripheral leptin sensitivity and may hold therapeutic promise (Moon et al, 2011;Müller et al, 2012;Matthias, 2014;Crujeiras et al, 2015;Park & Ahima, 2015). These leptin sensitisers target distinct neuroendocrine systems related to leptin signalling pathology.…”

Section: Multi-therapy Of Leptinmentioning

confidence: 99%

“…Nevertheless, overcoming resistance to the leptin therapy continues to challenge the researchers. In recent years some preclinical studies have surprisingly demonstrated that resistance to leptin can be reversed and the effects of leptin therapy can be amplified by several leptin sensitisers (Moon et al, 2011;Müller et al, 2012;Matthias, 2014;Crujeiras et al, 2015;Park & Ahima, 2015). Accordingly, it is the aim of this paper to critically discuss the plausible revival of leptin for obesity therapy with reference to research findings on various influencing factors contributing to the level of expression and secretion of leptin.…”

Section: Introductionmentioning

confidence: 99%

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Critically Discuss the Revival of Leptin for Obesity Therapy

Lo¹

2018

PSYCH

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Obesity has created a very serious public health problem, and World Health Organisation has actually warned that there is an urgent need for multinational cooperation to stem the rise of obesity. More than 20 years ago the discovery of Leptin, which is an adipocyte-secreted hormone and primarily acts on the hypothalamic neurons to activate the regulation of energy homeostasis, created much interest in its potential use for the treatment of obesity, but the hope was soon lost after leptin failed to counteract common diet-induced obesity. In recent years some preclinical studies have surprisingly demonstrated that resistance to leptin can be reversed and the effects of leptin therapy can be amplified by several leptin sensitisers. This paper will critically discuss the plausible revival of leptin for obesity therapy with reference to research findings on various influencing factors contributing to the level of expression and secretion of leptin.

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Leptin resistance in obesity: An epigenetic landscape

Cited by 201 publications

References 92 publications

Innate immunity in diabetes and diabetic nephropathy

Innate immunity in diabetes and diabetic nephropathy

Mice lacking have reduced signs of metabolic syndrome and non-alcoholic fatty liver disease

Critically Discuss the Revival of Leptin for Obesity Therapy

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