Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons

Sun, Jia; Gao, Yong; Yao, Ting; Huang, Yiru; He, Zhenyan; Kong, Xingxing; Yu, Kai; Wang, Rui Tao; Guo, Hongbo; Yan, Jiaqi; Chang, Yongsheng; Chen, Hong; Scherer, Philipp E.; Liu, Tiemin; Williams, Kevin W.

doi:10.1016/j.molmet.2016.08.007

Cited by 53 publications

(58 citation statements)

References 55 publications

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“…Similar to previous reports (Hill et al, 2008; Sohn et al, 2011), Pomc neurons that express LepRs were targeted from Pomc -hrGFP∷ LepR -cre-tdtomato (PLT) mice (Sohn et al, 2011; Sun et al, 2016; Williams et al, 2014) to test the acute cellular effects of leptin (Figures 3A to 3E). Leptin (100 nM) depolarized 70.6 % (12 out of 17) of wildtype Pomc neurons that express LepRs by 6.7 ± 0.5 mV (n=12, Figures 3F, 3J and supplemental table 1).…”

Section: Resultsmentioning

confidence: 85%

“…Male (4- 16-week-old) pathogen-free CamkIIα- cre, Pomc- creER T2 , Pomc- hrGFP∷ LepR -cre∷tdtomato (PLT), Pomc- hrGFP∷ Ht2Cr -cre∷tdtomato (P2CT), TrpC5KO, and TrpC5 fl/y (described below) mice (Berglund et al, 2013; Parton et al, 2007; Ramadori et al, 2010; Riccio et al, 2009; Sohn et al, 2011; Sun et al, 2016) were used for all experiments. All mice were housed under standard laboratory conditions (12 hr on/off; lights on at 7:00 a.m.) and temperature-controlled environment with food and water available ad libitum.…”

Section: Methodsmentioning

confidence: 99%

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TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

et al. 2017

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The molecular mechanisms underlying acute leptin and serotonin 2C receptor induced hypophagia remain unclear. Here we show that neuronal and pro-opiomelanocortin (Pomc)-specific loss of transient receptor potential cation 5 (TrpC5) subunits is sufficient to decrease energy expenditure and increase food intake resulting in elevated body weight. Deficiency of Trpc5 subunits in Pomc neurons was also sufficient to block the anorexigenic effects of leptin and serotonin 2C receptor (Ht2Cr) agonists. The loss of acute anorexigenic effects of these receptors was concomitant with a blunted electrophysiological response to both leptin and Ht2Cr agonists in arcuate Pomc neurons. We also demonstrate that the Ht2Cr agonist lorcaserin-induced improvements in glucose and insulin tolerance were blocked by TrpC5 deficiency in Pomc neurons. Together, our results link TrpC5 subunits in the brain with leptin- and serotonin 2C receptor-dependent changes in neuronal activity as well as energy balance, feeding behavior, and glucose metabolism.

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Section: Resultsmentioning

confidence: 85%

Section: Methodsmentioning

confidence: 99%

TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

et al. 2017

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“…The 7–9 weeks pathogen‐free male POMC‐hrGFP::LepR‐cre::td‐tomato (POMC‐hrGFP mice RRID: IMSR_JAX:006421; LepR‐cre mice RRID: IMSR_JAX:008320; td‐tomato mice RRID: IMSR_JAX:007908) (He et al ., ; Huang et al ., ; Sohn and Williams, ; Williams et al ., ), POMC‐hrGFP::LepR‐cre::td‐tomato::TRPC5 KO (TRPC5 KO mice RRID: IMSR_JAX:030804) (Gao et al ., ), POMC‐creER::IR‐flox::LepR‐flox::td‐tomato (POMC‐CreER t2 mice RRID: MGI: 5569339, IR‐flox mice RRID: IMSR_JAX:006955, LpeR‐flox mice RRID: IMSR_JAX:018989) and NPY‐hrGFP mice (NPY‐hrGFP mice RRID: IMSR_JAX:006417) (Sun et al, ) were used for all experiments. All mice were housed under standard laboratory conditions (12 h on/off; lights on at 7:00 a.m.) and temperature‐controlled environment.…”

Section: Methodsmentioning

confidence: 99%

“…Slice preparation and whole-cell recordings. Brain slices were prepared from young adult male mice (7-9 weeks old) as previously described (Sohn and Williams, 2012;Williams et al, 2014;Sun et al, 2016;Gao et al, 2017). Briefly, male mice were deeply anaesthetized with 7% chloral hydrate (i.p.)…”

Section: Electrophysiology Studiesmentioning

confidence: 99%

Acute effects of zinc and insulin on arcuate anorexigenic proopiomelanocortin neurons

Gao

Lieu

et al. 2019

British J Pharmacology

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Background and Purpose Acute insulin administration hyperpolarized, with concomitant decrease of firing rate, a subpopulation of arcuate proopiomelanocortin (POMC) and neuropeptide Y/agouti‐related peptide cells. This rapid effect on cellular activity has been proposed as a cellular correlate of insulin effects on energy balance and glucose homoeostasis. Recent evidence suggests that zinc in mammalian insulin formulations is required for the insulin‐induced inhibition of arcuate POMC neurons, while guinea pig insulin, which fails to bind zinc, activates POMC neurons in mice. Here, we tested the effects of zinc and insulin formations on arcuate POMC neurons. Experimental Approach Effects of zinc and insulin formulations were assessed through whole‐cell patch clamp recordings on transgenic mice in vitro. Key Results Insulin formulations containing zinc hyperpolarized POMC neurons. Zinc also hyperpolarized arcuate POMC neurons, albeit at much higher concentration than found in various insulin formulations. Chelation of zinc inhibited the zinc‐induced hyperpolarization of POMC neurons, whereas effects of insulin on POMC cellular activity were unchanged after chelation. Zinc‐free insulin also hyperpolarized arcuate POMC neurons. Insulin failed to hyperpolarize POMC neurons deficient for insulin receptors, suggesting that insulin receptors are required for these effects. Activation of POMC neurons by guinea pig insulin was independent of insulin receptors but was inhibited by PDGF receptor antagonism or loss of TRPC5 channel subunits. Conclusions and Implications Together, these findings suggest that insulin inhibited arcuate POMC neurons independent of zinc and highlights a possible role of putative PDGF receptors in the acute effects of guinea pig insulin.

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“…Leptin binds to the leptin receptor (Ob-Rb) in the ARC [91–95] and stimulates the cellular activity of POMC neurons while inhibiting the cellular activity of NPY/AgRP neurons [33]. Leptin or leptin receptor -deficient rodents and humans are obese due to hyperphagia and reduced energy expenditure [91,96].…”

Section: Hormonal Signalsmentioning

confidence: 99%

Melanocortin neurons: Multiple routes to regulation of metabolism

Shen

Yao

Kong

et al. 2017

Biochimica et Biophysica Acta (BBA) - Molecular Basis of Diseas

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The burden of disability, premature death, escalating health care costs and lost economic productivity due to obesity and its associated complications including hypertension, stroke, cardiovascular disease and type 2 diabetes is staggering [1,2]. A better understanding of metabolic homeostatic pathways will provide us with insights into the biological mechanisms of obesity and how to fundamentally address this epidemic [3–6]. In mammals, energy balance is maintained via a homeostatic system involving both peripheral and central melanocortin systems; changes in body weight reflect an unbalance of the energetic state [7–9]. Although the primary cause of obesity is unknown, there is significant effort to understand the role of the central melanocortin pathway in the brain as it has been shown that deficiency of proopiomelanocortin (POMC) [10,11] and melanocortin 4 receptors (MC4R) [12–15] in both rodents and humans results in severe hyperphagia and obesity [16–23]. In this review, we will summarize how the central melanocortin pathway helps regulate body mass and adiposity within a ‘healthy’ range through the ‘nutrient sensing’ network [24–28]. This article is part of a Special Issue entitled: Melanocortin Receptors - edited by Ya-Xiong Tao.

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Adiponectin potentiates the acute effects of leptin in arcuate Pomc neurons

Cited by 53 publications

References 55 publications

TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

TrpC5 Mediates Acute Leptin and Serotonin Effects via Pomc Neurons

Acute effects of zinc and insulin on arcuate anorexigenic proopiomelanocortin neurons

Melanocortin neurons: Multiple routes to regulation of metabolism

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