Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance

Özcan, Lale; Ergin, Ayse Seda; Lu, Amanda; Chung, Jason; Sarkar, Sumit; Nie, Duyu; Myers, Martin G.; Özcan, Umut

doi:10.1016/j.cmet.2008.12.004

Cited by 783 publications

(804 citation statements)

References 40 publications

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“…Heavy, lean sows that do not have sufficiently high lactation intake will likely have poorer longevity due to excessive weight loss. However, weight lossassociated stress can trigger increased appetite to compensate (Doucet et al, 2000) or alternatively inhibit appetite suppression (Ozcan et al, 2009), as shown in other species. Bergsma et al (2008) were the first to coin the term lactation efficiency (LE, defined as output/input), which combines the resources provided by the sow (through weight and fat loss) with lactation intake into an input variable, after accounting for sow maintenance requirements, and relates this input to piglet output.…”

Section: Discussionmentioning

confidence: 98%

Body development in sows, feed intake and maternal capacity. Part 2: gilt body condition before and after lactation, reproductive performance and correlations with lactation feed intake

Lewis

Bunter

2011

Animal

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Data on sow body weight (BW) and fatness (n 5 ,2250 pregnant sows) and reproductive data (including historical: n 5 ,18 000) were used to examine the genetic and phenotypic associations between body condition before and after farrowing, gestational outcomes, lactation feed intake and the gilts' ability to survive unculled to farrow in the second parity. Within-trait genetic correlations were very high between weight (0.77 6 0.06) and fat depth (0.91 6 0.04) recorded before farrowing and at weaning. Litter size traits were generally uncorrelated genetically with aspects of sow BW and body condition. However, genetic correlations indicated that sows producing heavier piglets at birth had litters with increased gain (0.36 6 0.16), and were characterised by greater weight (20.72 6 0.08) and fat change (20.19 6 0.15) during lactation, reflected to a lesser extent by lower weight (20.12 6 0.11) and fatness (20.17 6 0.10) at weaning. Genetic correlations (r a ) between reproductive traits and lactation feed intake were generally low, but favourable. However, lactation intake was positively correlated with measures of sow size (r a 5 ,0.55), such that selection for lactation feed intake would likely be accompanied by increased mature sow size. Phenotypic correlations (r p ) showed that sow survival to the second parity (FAR12) was positively influenced by litter size and fat depth at weaning, supporting attributes of increased fatness before farrowing, less weight loss during lactation and an increased lactation intake.

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Section: Discussionmentioning

confidence: 98%

Body development in sows, feed intake and maternal capacity. Part 2: gilt body condition before and after lactation, reproductive performance and correlations with lactation feed intake

Lewis

Bunter

2011

Animal

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“…Therefore, we suggest that SOCS-3 is a putative mechanism for the onset of leptin resistance in DIO rats. In addition to SOCS-3, other negative regulators of leptin signaling have been shown to be involved in the induction of leptin signaling in the central nervous system, such as PTP1B (2,20) and endoplasmic reticulum (ER) stress (31). Further work is required to determine whether PTP1B or proteins involved in ER stress are expressed in VAN and whether these mechanisms are involved in the development of leptin resistance in these neurons.…”

Section: Discussionmentioning

confidence: 99%

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Lartigue

Serre

Espero

et al. 2011

American Journal of Physiology-Endocrinology and Metabolism

154

142

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de Lartigue G, Barbier de la Serre C, Espero E, Lee J, Raybould HE. Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons. Am J Physiol Endocrinol Metab 301: E187-E195, 2011. First published April 26, 2011; doi:10.1152/ajpendo.00056.2011.-Ingestion of high-fat, high-calorie diets is associated with hyperphagia, increased body fat, and obesity. The mechanisms responsible are currently unclear; however, altered leptin signaling may be an important factor. Vagal afferent neurons (VAN) integrate signals from the gut in response to ingestion of nutrients and express leptin receptors. Therefore, we tested the hypothesis that leptin resistance occurs in VAN in response to a high-fat diet. Sprague-Dawley rats, which exhibit a bimodal distribution of body weight gain, were used after ingestion of a high-fat diet for 8 wk. Body weight, food intake, and plasma leptin levels were measured. Leptin signaling was determined by immunohistochemical localization of phosphorylated STAT3 (pSTAT3) in cultured VAN and by quantifaction of pSTAT3 protein levels by Western blot analysis in nodose ganglia and arcuate nucleus in vivo. To determine the mechanism of leptin resistance in nodose ganglia, cultured VAN were stimulated with leptin alone or with lipopolysaccharide (LPS) and SOCS-3 expression measured. SOCS-3 protein levels in VAN were measured by Western blot following leptin administration in vivo. Leptin resulted in appearance of pSTAT3 in VAN of low-fat-fed rats and rats resistant to diet-induced obesity but not diet-induced obese (DIO) rats. However, leptin signaling was normal in arcuate neurons. SOCS-3 expression was increased in VAN of DIO rats. In cultured VAN, LPS increased SOCS-3 expression and inhibited leptin-induced pSTAT3 in vivo. We conclude that VAN of diet-induced obese rats become leptin resistant; LPS and SOCS-3 may play a role in the development of leptin resistance.lipopolysaccharide; high-fat diet; suppressor of cytokine signaling-3 THE GUT PLAYS A CRUCIAL ROLE in sensing luminal contents that is important for the efficient digestion and absorption of ingested nutrients but also in integration of other physiological processes that regulate metabolism and energy expenditure, such as pancreatic ␤-cell function, hepatic function, and also food intake (34). In response to the presence or absence of food, enteroendocrine cells of the gut release anorexic or orexigenic hormones, respectively. The first site of integration of these signals occurs at the level of vagal afferent neurons (VAN), which project to and stimulate second-order neurons in the dorsal vagal complex of the hindbrain (27). VAN express receptors for many of the anorexigenic and orexigenic hormones released from the gut wall and mediate changes in gastrointestinal function and food intake in response to luminal nutrients (18).Leptin is a gut and adipose tissue-derived hormone that regulates a range of biological functions and processes, including energy intake and expenditure, body fat, neuroendocrine systems...

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“…Several mechanisms have been proposed to explain this resistance, including impaired leptin transport across the blood-brain barrier, endoplasmic reticulum stress and inflammation, as well as attenuated leptin signaling by SOCS3 and protein tyrosine phosphatase (PTP) (Ozcan et al, 2009;Zhang, Scarpace, 2009;Myers et al, 2012).…”

Section: Leptinmentioning

confidence: 99%

Obesity, inflammation, and insulin resistance

Martins

Oliveira

Cruz

et al. 2014

Braz. J. Pharm. Sci.

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White adipose tissue (WAT) is considered an endocrine organ. When present in excess, WAT can influence metabolism via biologically active molecules. Following unregulated production of such molecules, adipose tissue dysfunction results, contributing to complications associated with obesity. Previous studies have implicated pro-and anti-inflammatory substances in the regulation of inflammatory response and in the development of insulin resistance. In obese individuals, pro-inflammatory molecules produced by adipose tissue contribute to the development of insulin resistance and increased risk of cardiovascular disease. On the other hand, the molecules with anti-inflammatory action, that have been associated with the improvement of insulin sensitivity, have your decreased production. Imbalance of these substances contributes significantly to metabolic disorders found in obese individuals. The current review aims to provide updated information regarding the activity of biomolecules produced by WAT.Uniterms: Obesity. Inflammation. Adipose tissue. Adipokines. Insulin resistance.O tecido adiposo branco (WAT) é considerado um órgão endócrino, que, em excesso, é capaz de controlar o metabolismo, pela ação de moléculas biologicamente ativas. A produção desregulada destas substâncias pela disfunção do tecido adiposo pode contribuir para as complicações presentes na obesidade. As pesquisas atuais têm esclarecido fatores e mecanismos envolvidos na atuação de substâncias pró e anti-inflamatórias na modulação da inflamação e da resistência à insulina. Em indivíduos obesos, as moléculas pró-inflamatórias produzidas pelo tecido adiposo têm sido implicadas como fator contribuinte para o desenvolvimento da resistência à insulina e aumento do risco de doença cardiovascular. Por outro lado, as moléculas com ação anti-inflamatória, que atuam na melhora da sensibilidade à insulina, têm sua produção reduzida. O desequilíbrio entre essas substâncias contribui de forma significativa para as desordens metabólicas presente em indivíduos obesos. Assim, esta revisão visa a trazer informações atualizadas sobre a atuação de moléculas secretadas pelo tecido adiposo. Unitermos:Obesidade. Inflamação. Tecido adiposo. Adipocinas. Resistência à insulina.

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Endoplasmic Reticulum Stress Plays a Central Role in Development of Leptin Resistance

Cited by 783 publications

References 40 publications

Body development in sows, feed intake and maternal capacity. Part 2: gilt body condition before and after lactation, reproductive performance and correlations with lactation feed intake

Body development in sows, feed intake and maternal capacity. Part 2: gilt body condition before and after lactation, reproductive performance and correlations with lactation feed intake

Diet-induced obesity leads to the development of leptin resistance in vagal afferent neurons

Obesity, inflammation, and insulin resistance

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