Endocrinol Metab.  2013 Dec;28(4):288-296. 10.3803/EnM.2013.28.4.288.

Effects of Chronic Restraint Stress on Body Weight, Food Intake, and Hypothalamic Gene Expressions in Mice

• Jeong JY
• Lee DH
• Kang SS

• KMID: 2169307
• DOI: http://doi.org/10.3803/EnM.2013.28.4.288

Abstract

BACKGROUND
Stress affects body weight and food intake, but the underlying mechanisms are not well understood.
METHODS
We evaluated the changes in body weight and food intake of ICR male mice subjected to daily 2 hours restraint stress for 15 days. Hypothalamic gene expression profiling was analyzed by cDNA microarray.
RESULTS
Daily body weight and food intake measurements revealed that both parameters decreased rapidly after initiating daily restraint stress. Body weights of stressed mice then remained significantly lower than the control body weights, even though food intake slowly recovered to 90% of the control intake at the end of the experiment. cDNA microarray analysis revealed that chronic restraint stress affects the expression of hypothalamic genes possibly related to body weight control. Since decreases of daily food intake and body weight were remarkable in days 1 to 4 of restraint, we examined the expression of food intake-related genes in the hypothalamus. During these periods, the expressions of ghrelin and pro-opiomelanocortin mRNA were significantly changed in mice undergoing restraint stress. Moreover, daily serum corticosterone levels gradually increased, while leptin levels significantly decreased.
CONCLUSION
The present study demonstrates that restraint stress affects body weight and food intake by initially modifying canonical food intake-related genes and then later modifying other genes involved in energy metabolism. These genetic changes appear to be mediated, at least in part, by corticosterone.

Keyword

Restraint stress; Body weight; Eating; Hypothalamus; Microarray

MeSH Terms

Animals
Body Weight*
Corticosterone
DNA, Complementary
Eating*
Energy Metabolism
Gene Expression Profiling
Gene Expression*
Ghrelin
Humans
Hypothalamus
Leptin
Male
Mice*
Oligonucleotide Array Sequence Analysis
Pro-Opiomelanocortin
RNA, Messenger
Corticosterone
DNA, Complementary
Ghrelin
Leptin
Pro-Opiomelanocortin
RNA, Messenger

Figure

• 

  Fig. 1 Effects of restraint stress on body weight, food intake, serum corticosterone, and anxiety level. (A) Daily body weight and (B) food intake of mice exposed daily to 2 hours of restraint for 15 consecutive days. (C) Serum corticosterone levels were significantly increased in stressed mice (STR) at the end of the restraint stress period. (D) Stressed mice showed a significant reduction in frequency of open arm entry in the elevated plus maze test. Statistical differences were evaluated by (A, B) two-way analysis of variance and (C, D) Student unpaired t test. Data are presented as mean±SE. aP<0.05; bP<0.01 vs. control mice (CTL) (n=10 in each group).

• 

  Fig. 2 Reverse transcriptase polymerase chain reaction analysis of the altered gene expression identified from microarray analysis. The levels of hydroxysteroid (17-β) dehydrogenase 1 (Hsd17b1) and cytochrome P450, family 11, subfamily a, polypeptide 1 (Cyp11a1) mRNA were increased in stressed mice (STR), while glycoprotein hormones, α subunit (Cga) and growth hormone (Gh) mRNA levels were decreased. Statistical difference was evaluated by Student unpaired t test. Data are presented as mean±SE. aP<0.05; bP<0.01 vs. control mice (CTL) (n=6 in each group).

• 

  Fig. 3 Effects of restraint stress on hypothalamic gene expression and serum hormone levels. (A) Hypothalamic mRNA expression of ghrelin and (B) pro-opiomelanocortin (POMC) in mice exposed daily to 2 hours of restraint for 4 days. (C) Serum corticosterone and (D) leptin levels for mice exposed daily to 2 hours of restraint for 4 days. Statistical differences were evaluated by one-way analysis of variance and Dunnett t test. Data are presented as mean±SE. aP<0.05; bP<0.01 vs. control mice (n=6 in each group).

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