PMID- 23892476
OWN - NLM
STAT- MEDLINE
DCOM- 20131125
LR  - 20220311
IS  - 1945-7170 (Electronic)
IS  - 0013-7227 (Linking)
VI  - 154
IP  - 10
DP  - 2013 Oct
TI  - The gut microbiota reduces leptin sensitivity and the expression of the 
      obesity-suppressing neuropeptides proglucagon (Gcg) and brain-derived 
      neurotrophic factor (Bdnf) in the central nervous system.
PG  - 3643-51
LID - 10.1210/en.2012-2151 [doi]
AB  - The gut microbiota contributes to fat mass and the susceptibility to obesity. 
      However, the underlying mechanisms are not completely understood. To investigate 
      whether the gut microbiota affects hypothalamic and brainstem body fat-regulating 
      circuits, we compared gene expression of food intake-regulating neuropeptides 
      between germ-free and conventionally raised (CONV-R) mice. We found that CONV-R 
      mice had decreased expression of the antiobesity neuropeptide glucagon-like 
      peptide-1 (GLP-1) precursor proglucagon (Gcg) in the brainstem. Moreover, in both 
      the hypothalamus and the brainstem, CONV-R mice had decreased expression of the 
      antiobesity neuropeptide brain-derived neurotrophic factor (Bdnf). CONV-R mice 
      had reduced expression of the pro-obesity peptides neuropeptide-Y (Npy) and 
      agouti-related protein (Agrp), and increased expression of the antiobesity 
      peptides proopiomelanocortin (Pomc) and cocaine- and amphetamine-regulated 
      transcript (Cart) in the hypothalamus. The latter changes in neuropeptide 
      expression could be secondary to elevated fat mass in CONV-R mice. Leptin 
      treatment caused less weight reduction and less suppression of orexigenic Npy and 
      Agrp expression in CONV-R mice compared with germ-free mice. The hypothalamic 
      expression of leptin resistance-associated suppressor of cytokine signaling 3 
      (Socs-3) was increased in CONV-R mice. In conclusion, the gut microbiota reduces 
      the expression of 2 genes coding for body fat-suppressing neuropeptides, Gcg and 
      Bdnf, an alteration that may contribute to fat mass induction by the gut 
      microbiota. Moreover, the presence of body fat-inducing gut microbiota is 
      associated with hypothalamic signs of Socs-3-mediated leptin resistance, which 
      may be linked to failed compensatory body fat reduction.
FAU - Schele, Erik
AU  - Schele E
AD  - Sahlgrenska Academy at the University of Gothenburg, Institute of Neuroscience 
      and Physiology/Endocrinology Medicinaregatan 11, Goteborg-41390, Sweden. 
      john-olov.jansson@medic.gu.se.
FAU - Grahnemo, Louise
AU  - Grahnemo L
FAU - Anesten, Fredrik
AU  - Anesten F
FAU - Hallen, Anna
AU  - Hallen A
FAU - Backhed, Fredrik
AU  - Backhed F
FAU - Jansson, John-Olov
AU  - Jansson JO
LA  - eng
PT  - Comparative Study
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20130726
PL  - United States
TA  - Endocrinology
JT  - Endocrinology
JID - 0375040
RN  - 0 (Agouti-Related Protein)
RN  - 0 (Agrp protein, mouse)
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (Leptin)
RN  - 0 (Nerve Tissue Proteins)
RN  - 0 (Neuropeptide Y)
RN  - 0 (Recombinant Proteins)
RN  - 0 (Socs3 protein, mouse)
RN  - 0 (Suppressor of Cytokine Signaling 3 Protein)
RN  - 0 (Suppressor of Cytokine Signaling Proteins)
RN  - 0 (cocaine- and amphetamine-regulated transcript protein)
RN  - 55963-74-1 (Proglucagon)
RN  - 66796-54-1 (Pro-Opiomelanocortin)
SB  - IM
MH  - Adiposity
MH  - Agouti-Related Protein/genetics/metabolism
MH  - Animals
MH  - Brain Stem/metabolism
MH  - Brain-Derived Neurotrophic Factor/genetics/*metabolism
MH  - Central Nervous System/*metabolism
MH  - *Down-Regulation
MH  - Germ-Free Life
MH  - Hypothalamus/metabolism
MH  - Injections, Intraperitoneal
MH  - Intestines/*microbiology
MH  - Leptin/administration & dosage/blood/genetics/*metabolism
MH  - Male
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Nerve Tissue Proteins/genetics/metabolism
MH  - Neurons/*metabolism
MH  - Neuropeptide Y/genetics/metabolism
MH  - Pro-Opiomelanocortin/genetics/metabolism
MH  - Proglucagon/genetics/*metabolism
MH  - Recombinant Proteins/administration & dosage/metabolism
MH  - Suppressor of Cytokine Signaling 3 Protein
MH  - Suppressor of Cytokine Signaling Proteins/genetics/metabolism
EDAT- 2013/07/31 06:00
MHDA- 2013/12/16 06:00
CRDT- 2013/07/30 06:00
PHST- 2013/07/30 06:00 [entrez]
PHST- 2013/07/31 06:00 [pubmed]
PHST- 2013/12/16 06:00 [medline]
AID - en.2012-2151 [pii]
AID - 10.1210/en.2012-2151 [doi]
PST - ppublish
SO  - Endocrinology. 2013 Oct;154(10):3643-51. doi: 10.1210/en.2012-2151. Epub 2013 Jul 
      26.