title: Deletion of Nhlh2 results in a defective torpor response and reduced Beta adrenergic receptor expression in adipose tissue.
abstract: BACKGROUND
  Mice with a targeted deletion of the basic helix-loop-helix transcription factor, Nescient Helix-Loop-Helix 2 (Nhlh2), display adult-onset obesity with significant increases in their fat depots, abnormal responses to cold exposure, and reduced spontaneous physical activity levels. These phenotypes, accompanied by the hypothalamic expression of Nhlh2, make the Nhlh2 knockout (N2KO) mouse a useful model to study the role of central nervous system (CNS) control on peripheral tissue such as adipose tissue.
  
  
  METHODS
  Differences in body temperature and serum analysis of leptin were performed in fasted and ad lib fed wild-type (WT) and N2KO mice. Histological analysis of white (WAT) and brown adipose tissue (BAT) was performed. Gene and protein level expression of inflammatory and metabolic markers were compared between the two genotypes.
  
  
  RESULTS
  We report significant differences in serum leptin levels and body temperature in N2KO mice compared with WT mice exposed to a 24-hour fast, suggestive of a defect in both white (WAT) and brown adipose tissue (BAT) function. As compared to WT mice, N2KO mice showed increased serum IL-6 protein and WAT IL-6 mRNA levels. This was accompanied by slight elevations of mRNA for several macrophage markers, including expression of macrophage specific protein F4/80 in adipose, suggestive of macrophage infiltration of WAT in the mutant animals. The mRNAs for beta3-adrenergic receptors (beta3-AR), beta2-AR and uncoupling proteins were significantly reduced in WAT and BAT from N2KO mice compared with WT mice.
  
  
  CONCLUSIONS
  These studies implicate Nhlh2 in the central control of WAT and BAT function, with lack of Nhlh2 leading to adipose inflammation and altered gene expression, impaired leptin response to fasting, all suggestive of a deficient torpor response in mutant animals.
authors.affiliation: Department of Human Nutrition, Foods and Exercise, Virginia Polytechnic Institute and State University, Blacksburg, Virginia, United States of America.
authors.forename: Umesh D
authors.initials: UD
authors.lastname: Wankhade
authors.forename: Kristen R
authors.initials: KR
authors.lastname: Vella
authors.forename: Dana L
authors.initials: DL
authors.lastname: Fox
authors.forename: Deborah J
authors.initials: DJ
authors.lastname: Good
mesh_terms: D052437:Adipocytes, Brown / Q000166:cytology / Q000378:metabolism; D052438:Adipocytes, White / Q000166:cytology / Q000378:metabolism; D000273:Adipose Tissue / Q000166:cytology / Q000378:metabolism*; D000818:Animals; D000943:Antigens, Differentiation / Q000378:metabolism; D051792:Basic Helix-Loop-Helix Proteins / Q000172:deficiency* / Q000235:genetics*; D015415:Biomarkers / Q000378:metabolism; D001831:Body Temperature; D004734:Energy Metabolism; D005215:Fasting; D017353:Gene Deletion; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation; D055786:Gene Knockout Techniques; D007249:Inflammation / Q000235:genetics; D020738:Leptin / Q000378:metabolism; D008264:Macrophages / Q000378:metabolism; D008297:Male; D051379:Mice; D011943:Receptors, Adrenergic, beta / Q000235:genetics / Q000378:metabolism*
chemical_list: D000943:Antigens, Differentiation; D051792:Basic Helix-Loop-Helix Proteins; D015415:Biomarkers; D020738:Leptin; D011943:Receptors, Adrenergic, beta; C484104:Nhlh2 protein, mouse; C036763:monocyte-macrophage differentiation antigen
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