Featured Articles

Volume 27 | September 2019

Adipocyte Gs signaling regulates glucose homeostasisG protein coupled receptors (GPCRs) expressed in white and brown adipose tissue have pleiotropic effects on energy and glucose homeostasis. There are four main families of G proteins: Gi/Go, Gq, Gs, and G12. In rodents, most of the positive effects of the sympathetic nervous system on adipose tissue are attributed to Gs-coupled beta 3 adrenergic receptors located at the surface of adipocytes. Caron et al. used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs), chemogenetically-engineered proteins that allow spatial and temporal control of G protein signaling in vivo. They report that Gs, but not Gi signaling in adipocytes is a potent regulator of systemic glucose homeostasis.

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Impact of dietary sucrose depends on mode of ingestion: liquid or solid The causes for the current obesity epidemic are unclear. One possible risk factor is a high consumption of sucrose, which may be in the form of sugar-sweetened beverages (SSB). Togo and colleagues studied the impact of high sugar diets with different forms of delivery: solid, pelleted sucrose or sucrose dissolved in the drinking water. They found that liquid sucrose exposure contributed to higher energy consumption leading to greater body weight and body fat. Mice exposed to equivalent levels of sucrose in the solid diet were leaner and metabolically healthier than their counterparts exposed to liquid sucrose. These results strongly suggest that the consumption of SSB is an important factor that can lead to obesity and metabolic disease.

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Phosphatidylserine decarboxylase is critical for skeletal muscle maintenance Phosphatidylethanolamine (PE) is the second most abundant phospholipid in mammals. The majority of PE is synthesized by two distinct pathways: the CDP-ethanolamine branch of the Kennedy pathway and decarboxylation of phosphatidylserine (PS) by the enzyme PS decarboxylase (PSD) located in the mitochondria. The PSD pathway is required to maintain mitochondrial structure and function and essential for life. Selathurai et al. studied the PSD pathway in muscle and found that it is important for PE synthesis in skeletal muscle and is required for maintenance of mitochondrial integrity and muscle mass. This reveals the role of mitochondria in maintaining skeletal muscle homeostasis.

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Evaporative cooling provides a major metabolic energy sink Thermogenesis could be harnessed to prevent obesity, which makes it important to understand sources of heat loss to maintain normothermia. Trans-epidermal water loss (TEWL) through perspiration is a cooling mechanism for over-heated mammalian bodies, but also occurs at low ambient temperatures. Kasza and colleagues calculated the energy dissipation created by evaporative cooling through mouse skin and show that increased rates of evaporative cooling account for increased energy expenditure reported in mouse strains with deficient lipid layers. They also show that obese mice show lower trans-epidermal water loss. This raises the possibility that evaporative cooling could be a significant player in energy expenditure to avoid obesity.

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GDF10 blocks PPARγ activation to protect against liver injury Growth differentiation factor 10 (GDF10) is an atypical member of the transforming growth factor β superfamily. It has been shown that that in vitro knockdown of GDF10 enhances adipogenesis and that transgenic mice overexpressing GDF10 are protected against diet-induced obesity and insulin resistance. Platko, Lebeau, et al. studied the impact of GDF10 on the liver. Their findings suggest that circulating GDF10 plays a critical role as a regulator of hepatic PPARγ during conditions of dietary stress and that GDF10 is capable of attenuating the progression of steatosis to steatohepatitis.

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ATGL-1 mediates longevity effects in C. elegans Animal lifespan is increased by fasting and a reduction of insulin/IGF signaling (IIS), an effect that is conserved from nematodes to humans. Two major "signaling nodes", Forkhead box O1 (FoxO1)- and Target Of Rapamycin Complex 1 (TORC1)-centered, are responsible for the effect of nutrients and IIS on the lifespan. Zaarur et al. recently found that FoxO1 and mTORC1 control the rates of lipolysis in mammalian cells by regulating expression of adipose triglyceride lipase (ATGL). Here, they use the nematode C. elegans to show that ATGL is the common mediator of the fasting and IIS longevity effects.

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Gs signaling in adipocytes causes striking metabolic improvements Like most other cell types, adipocytes express many G protein-coupled receptors (GPCRs). Each GPCR displays a distinct G protein coupling preference, activating either Gs- Gi-, or Gq-type G proteins which are linked to specific signaling pathways. At present, little is known about how activation of these various GPCR/G protein pathways affects glucose homeostasis. Wang et al. used Designer Receptors Exclusively Activated by Designer Drugs (DREADDs) that can only be activated by an exogenously administered drug to elucidate the impact of Gs signaling in adipocytes. In agreement with the report by Caron et al., they found improved glucose homeostasis upon Gs activation.

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The 60 Second Metabolist
In this section authors briefly report on their work recently published in Molecular Metabolism.

Watch the most recent interview by clicking the video still. The link "referring article" directs you to this author's publication.



Ildiko Kasza, Caroline Alexander
University of Wisconsin-Madison, United States
Referring article

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