Recent CIG publications Archive

Handb Exp Pharmacol. 2012;(209):277-94.

Thorens B.

Source

Center for Integrative Genomics, University of Lausanne, Switzerland. Bernard.thorens@unil.ch

Abstract

The brain, and in particular the hypothalamus and brainstem, have been recognized for decades as important centers for the homeostatic control of feeding, energy expenditure, and glucose homeostasis. These structures contain neurons and neuronal circuits that may be directly or indirectly activated or inhibited by glucose, lipids, or amino acids. The detection by neurons of these nutrient cues may become deregulated, and possibly cause metabolic diseases such as obesity and diabetes. Thus, there is a major interest in identifying these neurons, how they respond to nutrients, the neuronal circuits they form, and the physiological function they control. Here I will review some aspects of glucose sensing by the brain. The brain is responsive to both hyperglycemia and hypoglycemia, and the glucose sensing cells involved are distributed in several anatomical sites that are connected to each other. These eventually control the activity of the sympathetic or parasympathetic nervous system, which regulates the function of peripheral organs such as liver, white and brown fat, muscle, and pancreatic islets alpha and beta cells. There is now evidence for an extreme diversity in the sensing mechanisms used, and these will be reviewed.

Am J Physiol Endocrinol Metab. 2012 Apr 24. [Epub ahead of print]

Ge X, Vajjala A, McFarlane C, Wahli W, Sharma M, Kambadur R.

Source

1Nanyang Technological University.

Abstract

Smad3 is a key intracellular signaling mediator for both TGF-β and Myostatin, two major regulators of skeletal muscle growth. Previous published work has revealed pronounced muscle atrophy together with impaired Satellite Cell (SC) functionality in Smad3-null muscles. In the present study, we have further validated a role for Smad3 signaling in skeletal muscle regeneration. Here, we show that Smad3-null mice had incomplete recovery of muscle weight and myofiber size after muscle injury. Histological/Immunohistochemical analysis suggested impaired inflammatory response and reduced number of activated myoblasts during the early stages of muscle regeneration in the M. tibialis anterior muscle of Smad3-null mice. Nascent myofibers formed after muscle injury were also reduced in number. Moreover, Smad3-null regenerated muscle had decreased oxidative enzyme activity and impaired mitochondrial biogenesis, evident by the down-regulation of the gene encoding TFAM, a master regulator of mitochondrial biogenesis. Consistent with known Smad3 function, reduced fibrotic tissue formation was also seen in regenerated Smad3-null muscle. In conclusion, Smad3 deficiency leads to impaired muscle regeneration, which underscores an essential role of Smad3 in post-natal myogenesis. Given the negative role of Myostatin during muscle regeneration, the increased expression of Myostatin observed in Smad3-null muscle may contribute to the regeneration defects.

1. David Gfeller,
2. Olivier Michielin,
3. Vincent Zoete

Article first published online: 14 APR 2012

DOI: 10.1002/jcc.22982

Copyright © 2012 Wiley Periodicals, Inc.