Abstract
Leptin is an adipokine that regulates body weight by decreasing appetite and increasing energy expenditure. Besides the effects on food intake, leptin can regulate energy expenditure at least in part by modulating thermogenesis. Many of the effects of leptin are attributable to action in the central nervous system, particularly in the hypothalamus. Common forms of obesity are associated with increased leptin levels and a failure to suppress feeding and mediate weight loss in response to exogenous leptin. This apparent leptin ineffectiveness defines a state of so-called leptin resistance. We examined the effect of leptin on core body temperature in rats with normal weight and diet-induced obesity (DIO), as well as thermoregulatory interactions between leptin and GABAB-agonist and an antagonist. We found that leptin retains the ability to induce hyperthermic effect in rats with DIO. Additionally, temperature responses produced by GABAB agonist and antagonist are altered in a state of obesity and by administration of leptin. We evaluated whether the medial preoptic area of the anterior hypothalamus (MPA) still remains sensitive to leptin action during DIO. Using extracellular recordings of neurons and phospho-signal transducer and the activator of transcription 3 (pSTAT3) immunohistochemistry, we have provided strong evidence that leptin signaling in the MPA is impaired in obese rats. We believe that leptin resistance in the MPA may play a role in the pathogenesis of obesity and obesity-related disease states.
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Abbreviations
- ACSF:
-
Artificial cerebrospinal fluid
- ARC:
-
Arcuate nucleus of the hypothalamus
- CAF:
-
Cafeteria diet
- DIO:
-
Diet-induced obesity
- DMH:
-
Dorsomedial hypothalamus
- GABA:
-
Gamma-aminobutyric acid
- JAK2:
-
Janus kinase 2
- LHA:
-
Lateral hypothalamic area
- MPA:
-
Medial preoptic area
- NTS:
-
Nucleus of the solitary tract
- PI3K:
-
Phosphoinositide 3-kinase
- PMN:
-
Premammilary nucleus
- PO/AH:
-
Preoptic area of the anterior hypothalamus
- pSTAT3:
-
Phosphorylated STAT3
- PVN:
-
Paraventricular nucleus of the hypothalamus
- SC:
-
Standard chow
- SOCS3:
-
Suppressor of cytokine signaling 3
- STAT3:
-
Signal transducer and activator of transcription 3
- VMH:
-
Ventromedial hypothalamus
- VTA:
-
Ventral tegmental area
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Hristov, M., Landzhov, B., Nikolov, R. et al. Central, but not systemic, thermoregulatory effects of leptin are impaired in rats with obesity: interactions with GABAB agonist and antagonist. Amino Acids 51, 1055–1063 (2019). https://doi.org/10.1007/s00726-019-02746-x
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DOI: https://doi.org/10.1007/s00726-019-02746-x