Featured Articles

Volume 3 | No. 2 | March 2014

Obesity risk gene and postprandial responseThe strongest genetic determinant, with the highest population-attributable risk of increased body weight known today, is variation in the FTO (fat mass- and obesity-associated) gene. Heni and colleagues now provide novel insights into how genetic background influences body weight via postprandial alteration of brain activity.

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A novel mitochondrial uncouplerA possible factor limiting the use of available protonophore uncouplers is their unwanted activity at other membranes such as the plasma membrane. Kenwood and colleagues now report the identification of a novel, highly potent mitochondrial uncoupler, named BAM15, which is selective for mitochondria and does not depolarize the plasma membrane, enabling a sustained maximal rate of mitochondrial respiration with low cytotoxicity.

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Open the door for insulin resistanceAbnormal mitochondrial structure and/or function are correlated with insulin resistance in skeletal muscle. The results of Taddeo and colleagues show that opening of the mitochondrial permeability transition pore (mPTP) is required for insulin resistance in skeletal muscle. Inhibition of the mPTP improves skeletal muscle glucose clearance and prevents from insulin resistance.

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Angptl4 – the gatekeeper in intestinal lipid uptakeTriglycerides are digested in the gastrointestinal tract through the action of several lipases. However, little is known about the regulation of the activity of pancreatic lipase. Mattijssen and colleagues now describe a novel function of Angptl4 in the regulation of lipid metabolism. By acting as a gatekeeper in the regulation of intestinal lipid uptake, Angptl4 decreases the amount of lipid being harvested from the ingested food and protects against enterocyte lipid overload.

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Lipin-1 and lipin-3 together determine adiposityLipins are the primary source of phosphatidate phosphatase (PAP) activity in glycerolipid biosynthesis, but the extent to which each of the three family members contributes to PAP activity, triacylglycerol storage, and lipid homeostasis in different tissues has been unclear. The results of Csaki and colleagues provide evidence that lipin-3 is required for optimal adipocyte differentiation and that lipin-1 and lipin-3 cooperatively influence adipose PAP activity and adiposity.

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TSC22D1 – a new target for beneficial manipulation of HDLHigh-density lipoprotein (HDL) cholesterol concentration is inversely proportional to the risk for developing cardiovascular disease and type 2 diabetes. Jaeger and colleagues show that specific targeting of the hepatic transforming growth factor-β1 stimulated clone D1 (TSC22D1) complex might represent an attractive therapeutic mode to control HDL cholesterol levels under conditions of diabetes/obesity-related energy surplus and loss of atheroprotection.

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Hippocampus and energy balanceHypothalamic fatty acid sensing plays a role in the regulation of energy balance, including insulin secretion and action, hepatic glucose production and food intake. The study of Picard and colleagues highlights on the role of hippocampal lipoprotein lipase in the regulation of energy balance depending on de novo ceramide biosynthesis pathway and the modulation of the parasympathetic nervous system activity.

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Estrogen deficiency and diabesityEstrogen deficiency increases the risk for metabolic syndrome and type 2 diabetes. The results of Kim and colleagues show that the tissue-selective estrogen complex combining conjugated estrogen (CE) to the selective estrogen receptor modulator bazedoxifene prevents estrogen deficiency-induced adiposity and insulin resistance as efficiently as CE alone and without causing endometrial hyperplasia.

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GLP-1 is not involved in effects of gastric bypassClinical observations suggest that the gut-derived peptide hormone glucagon-like peptide-1 (GLP-1) is responsible for the beneficial effects of Roux-en-Y gastric bypass (RYGB) on glucose and energy homeostasis. Using two models of functional GLP-1 deficiency, Mokadem and colleagues demonstrate that GLP-1 is unlikely to mediate the major effects of RYGB on body weight and glucose homeostasis.

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Glucagon action in the hypothalamus and the role of KATP channelsA role of glucagon action in the mediobasal hypothalamus was recently documented, in contrast to the hormone's hepatic stimulatory effect, to lower glucose production. The results of Abraham and colleagues show that glucagon action in the hypothalamus signals through a lipid-sensing independent but KATP channel dependent pathway to lower glucose production.

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AVP neurons regulate feedingArginine vasopressin (AVP) is robustly expressed in parvocellular cells of the paraventricular nucleus of the hypothalamus (PVH), but its physiologic function within the brain, and specifically in energy balance, has not been fully defined. Pei and colleagues now demonstrate that PVH-AVP neurons are activated by melanocortin agonists and that direct activation of PVH-AVP neurons suppresses food intake.

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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.



Jennifer Lee
University of Toronto, Canada
Referring article

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