Featured Articles

Volume 4 | No. 3 | March 2015

Metabolic modeling of muscle metabolism

Nogiec and colleagues developed an in silico model of muscle metabolism that incorporates reciprocal modulation of lipid oxidation and glucose uptake in order to model the fasted to fed transition. The findings suggest that metabolic phenotypes linked to IR are not likely to arise from a single gene defect, but from dysregulation of metabolic adaptations to energy/nutrient stress at several key nodes.

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NPY signaling in early osteoblasts controls glucose homeostasis

Lee and colleagues demonstrate that NPY signaling via osteoblastic Y1 receptors is important for controlling bone mass and contributing to the control of insulin secretion and glucose homeostasis in mice via a novel factor. The research explores one of the most novel developments in bone biology, the identification of a regulatory axis from the osteoblast to the pancreatic b-cell.

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Genetic determination of the ghrelin-dependent bone remodeling

Ma and colleagues show that ghrelin regulates bone remodeling through Ghsr in osteoblasts rather than via the central nervous system. Ghrelin uses osteoblastic CREB and Runx2 to regulate osteoblast differentiation.

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High-calorie (HC) diet exacerbates prostate neoplasia in mice

Liu and colleagues show that HC diet promotes prostate cancer progression in a model of genetic susceptibility resulting from loss of Pten, a tumor suppressor gene. Mechanistically, this advanced neoplastic state can be mediated, in part, by enhanced activation of Akt and MAPK pathways and induction of de novo lipogenesis in prostate in the presence of enhanced insulin response to chronically elevated insulin levels.

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Seipin oligomers can interact directly with AGPAT2 and lipin 1

Talukder and colleagues demonstrate that seipin dodecamers can act as scaffolds for multiple proteins and can simultaneously bind both AGPAT2 and lipin 1, two critical regulators of adipogenesis. This work provides the first direct, physical and mechanistic link between seipin and AGPAT2, the two proteins whose disruption most commonly causes severe generalized lipodystrophy in humans.

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Central nervous system neuropeptide Y regulates mediators of hepatic phospholipid remodeling

Rojas and colleagues reveal that NPY signaling is important in the central regulation of hepatic lipoprotein metabolism. In lean fasted rats, CNS NPY signaling modulates the expression and/or activity of key hepatic regulatory proteins (SCD-1, ARF-1, and lipin-1) involved in remodeling of PL and VLDL maturation. These effects of central NPY are mediated by NPY Y1 receptor signaling and sympathetic innervation of the liver.

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Decreased expression of hepatic glucokinase in type 2 diabetes

Haeusler and colleagues measure gene expression in human liver biopsies. They find glucokinase decreased in diabetic patients with HbA1c > 7.0% and glucokinase mRNA negatively correlated with HbA1c and fasting glucose.

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Leptin recruits Creb-regulated transcriptional coactivator 1 to improve hyperglycemia

Kim and colleagues define Crtc1 as a transcriptional effector that is necessary for leptin to alleviate hyperglycemia but not glucagon secretion in experimental diabetes. The data highlight a role for leptin-Crtc1 signaling in regulating metabolic gene expression in liver and soleus and improving glucose uptake into iBAT and heart.

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SOCS3 deficiency in leptin receptor-expressing cells

Zampieri and colleagues identify the increased hypothalamic expression of SOCS3 as a key mechanism responsible for inducing pregnancy-induced leptin resistance and metabolic adaptations. SOCS3 KO mice are protected against long-term postpartum fat retention and gestational diabetes mellitus.

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Increased biogenesis of glucagon-containing secretory granules and glucagon secretion

Li and colleagues show that BIG3 is highly expressed in alpha-cells, and its loss leads to elevated glucagon production and enhanced secretion at single islet and whole organism level. Together with previous studies, a conserved function of BIG3 in regulating secretory granule biogenesis and hormone secretion in pancreatic islets has emerged.

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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.

Marc Reitman
National Institutes of Health (NIH), Bethesda, USA
Referring article

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