Hypothalamic c-fos-like immunoreactivity in high-fat diet-induced obese and resistant mice.
Some C57Bl/6 mice become obese, whereas others remain lean when raised on a high-fat diet. The mechanisms underlying this interindividual susceptibility to diet-induced obesity remain unknown. Because hypothalamus plays a major role in the regulation of body weight, this study was conducted to identify the differences of hypothalamic neuronal activity between diet-induced obese and diet-resistant mice. Using c-fos as a marker, this study showed that diet-induced obese mice significantly increased c-fos-like immunoreactive neurons in the dorsal part of lateral hypothalamus (+183%) and dorsomedial hypothalamic nucleus (+87.5%) compared with diet-resistant mice. Furthermore, switching from high fat to low fat, or high n-3 polyunsaturated fatty acid diet, significantly decreased body weight gain (-35.7% and -31.0%), overall fat storage (-63.4% and -59.6%), and c-fos-like immunoreactive neurons in the dorsal part of lateral hypothalamus (-76.5% and -64.7%) and dorsomedial hypothalamic nucleus (-73.3% and -56.7%) in diet-induced obese mice, respectively. The present study also showed that the ratio of serum leptin/fat mass was threefold higher in the diet-resistant mice than in the diet-induced obese mice, which may be responsible for the less fat storage in the diet-resistant mice. The current data further confirm that the increased neuronal activity in the key autonomic regulatory centers may contribute to the excessive fat storage in diet-induced obese mice. Moreover, both high-fat diet-induced excessive fat storage and the altered hypothalamic neuronal activity may be largely corrected by reducing dietary fat content or replacing it with non-obesogenic fat.
Xin
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Metabolic Research Center, Department of Biomedical Science, University of Wollongong, NSW, Australia.
Storlien
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LH
Huang
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XF
D000818:Animals; D001835:Body Weight / Q000502:physiology; D018752:Diet, Fat-Restricted; D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D004198:Disease Susceptibility / Q000378:metabolism; D004302:Dorsomedial Hypothalamic Nucleus / Q000166:cytology / Q000378:metabolism; D002149:Energy Intake / Q000502:physiology; D015525:Fatty Acids, Omega-3 / Q000008:administration & dosage*; D007031:Hypothalamus / Q000166:cytology / Q000378:metabolism*; D020738:Leptin / Q000097:blood; D050356:Lipid Metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009474:Neurons / Q000166:cytology / Q000378:metabolism; D009765:Obesity / Q000097:blood / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000378:metabolism*
D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D015525:Fatty Acids, Omega-3; D020738:Leptin; D016760:Proto-Oncogene Proteins c-fos