Abstract
Hunger-sensing agouti-related peptide (AgRP) neurons ensure survival by adapting metabolism and behavior to low caloric environments. This adaption is accomplished by consolidating food intake, suppressing energy expenditure, and maximizing fat storage (nutrient partitioning) for energy preservation. The intracellular mechanisms responsible are unknown. Here we report that AgRP carnitine acetyltransferase (Crat) knockout (KO) mice exhibited increased fatty acid utilization and greater fat loss after 9 d of calorie restriction (CR). No differences were seen in mice with ad libitum food intake. Eleven days ad libitum feeding after CR resulted in greater food intake, rebound weight gain, and adiposity in AgRP Crat KO mice compared with wild-type controls, as KO mice act to restore pre-CR fat mass. Collectively, this study highlights the importance of Crat in AgRP neurons to regulate nutrient partitioning and fat mass during chronically reduced caloric intake. The increased food intake, body weight gain, and adiposity in KO mice after CR also highlights the detrimental and persistent metabolic consequence of impaired substrate utilization associated with CR. This finding may have significant implications for postdieting weight management in patients with metabolic diseases.
| Original language | English |
|---|---|
| Pages (from-to) | 6923-6933 |
| Number of pages | 11 |
| Journal | FASEB Journal |
| Volume | 32 |
| Issue number | 12 |
| DOIs | |
| Publication status | Published - 1 Dec 2018 |
Keywords
- Body composition
- Feeding behavior
- Metabolic flexibility
- Rebound weight gain
- RER
Cite this
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Carnitine acetyltransferase (Crat) in hunger-sensing AgRP neurons permits adaptation to calorie restriction. / Reichenbach, Alex; Stark, Romana; Mequinion, Mathieu; Lockie, Sarah H.; Lemus, Moyra B.; Mynatt, Randall L.; Luquet, Serge; Andrews, Zane B.
In: FASEB Journal, Vol. 32, No. 12, 01.12.2018, p. 6923-6933.Research output: Contribution to journal › Article › Research › peer-review
TY - JOUR
T1 - Carnitine acetyltransferase (Crat) in hunger-sensing AgRP neurons permits adaptation to calorie restriction
AU - Reichenbach, Alex
AU - Stark, Romana
AU - Mequinion, Mathieu
AU - Lockie, Sarah H.
AU - Lemus, Moyra B.
AU - Mynatt, Randall L.
AU - Luquet, Serge
AU - Andrews, Zane B.
PY - 2018/12/1
Y1 - 2018/12/1
N2 - Hunger-sensing agouti-related peptide (AgRP) neurons ensure survival by adapting metabolism and behavior to low caloric environments. This adaption is accomplished by consolidating food intake, suppressing energy expenditure, and maximizing fat storage (nutrient partitioning) for energy preservation. The intracellular mechanisms responsible are unknown. Here we report that AgRP carnitine acetyltransferase (Crat) knockout (KO) mice exhibited increased fatty acid utilization and greater fat loss after 9 d of calorie restriction (CR). No differences were seen in mice with ad libitum food intake. Eleven days ad libitum feeding after CR resulted in greater food intake, rebound weight gain, and adiposity in AgRP Crat KO mice compared with wild-type controls, as KO mice act to restore pre-CR fat mass. Collectively, this study highlights the importance of Crat in AgRP neurons to regulate nutrient partitioning and fat mass during chronically reduced caloric intake. The increased food intake, body weight gain, and adiposity in KO mice after CR also highlights the detrimental and persistent metabolic consequence of impaired substrate utilization associated with CR. This finding may have significant implications for postdieting weight management in patients with metabolic diseases.
AB - Hunger-sensing agouti-related peptide (AgRP) neurons ensure survival by adapting metabolism and behavior to low caloric environments. This adaption is accomplished by consolidating food intake, suppressing energy expenditure, and maximizing fat storage (nutrient partitioning) for energy preservation. The intracellular mechanisms responsible are unknown. Here we report that AgRP carnitine acetyltransferase (Crat) knockout (KO) mice exhibited increased fatty acid utilization and greater fat loss after 9 d of calorie restriction (CR). No differences were seen in mice with ad libitum food intake. Eleven days ad libitum feeding after CR resulted in greater food intake, rebound weight gain, and adiposity in AgRP Crat KO mice compared with wild-type controls, as KO mice act to restore pre-CR fat mass. Collectively, this study highlights the importance of Crat in AgRP neurons to regulate nutrient partitioning and fat mass during chronically reduced caloric intake. The increased food intake, body weight gain, and adiposity in KO mice after CR also highlights the detrimental and persistent metabolic consequence of impaired substrate utilization associated with CR. This finding may have significant implications for postdieting weight management in patients with metabolic diseases.
KW - Body composition
KW - Feeding behavior
KW - Metabolic flexibility
KW - Rebound weight gain
KW - RER
UR - http://www.scopus.com/inward/record.url?scp=85057548512&partnerID=8YFLogxK
U2 - 10.1096/fj.201800634R
DO - 10.1096/fj.201800634R
M3 - Article
AN - SCOPUS:85057548512
VL - 32
SP - 6923
EP - 6933
JO - FASEB Journal
JF - FASEB Journal
SN - 0892-6638
IS - 12
ER -