scholarly journals Amylin/Calcitonin Receptor–Mediated Signaling in POMC Neurons Influences Energy Balance and Locomotor Activity in Chow-Fed Male Mice

Diabetes ◽  
2020 ◽  
Vol 69 (6) ◽  
pp. 1110-1125 ◽  
Author(s):  
Bernd Coester ◽  
Christina Koester-Hegmann ◽  
Thomas A. Lutz ◽  
Christelle Le Foll
2020 ◽  
Author(s):  
E. Matthew Morris ◽  
Roberto D. Noland ◽  
Michael E. Ponte ◽  
Michelle L. Montonye ◽  
Julie A. Christianson ◽  
...  

AbstractCentral integration of peripheral neural signals is one mechanism by which systemic energy homeostasis is regulated. Previous work described increased acute food intake following chemical reduction of hepatic fatty acid oxidation and ATP levels, which was prevented by common hepatic branch vagotomy (HBV). However, possible offsite actions of the chemical compounds confound the precise role of liver energy metabolism. Herein, we used a liver-specific PGC1a heterozygous (LPGC1a) mouse model, with associated reductions in mitochondrial fatty acid oxidation and respiratory capacity, to assess the role of liver energy metabolism in systemic energy homeostasis. LPGC1a male mice have 70% greater high-fat/high-sucrose (HFHS) diet-induced weight gain and 35% greater positive energy balance compared to wildtype (WT) (p<0.05). The greater energy balance was associated with altered feeding behavior and lower activity energy expenditure during HFHS in LPGC1a males. Importantly, no differences in HFHS-induced weight gain or energy metabolism was observed between female WT and LPGC1a mice. WT and LPGC1a mice underwent sham or HBV to assess whether vagal signaling was involved in HFHS-induced weight gain of male LPGC1a mice. HBV increased HFHS-induced weight gain (85%, p<0.05) in male WT, but not LPGC1a mice. As above, sham LPGC1a males gain 70% more weight during short-term HFHS feeding than sham WT (p<0.05). These data demonstrate a sexspecific role of reduced liver energy metabolism in acute diet-induced weight gain, and the need of more nuanced assessment of the role of vagal signaling in short-term diet-induced weight gain.Key Points SummaryReduced liver PGC1a expression results in reduced mitochondrial fatty acid oxidation and respiratory capacity in male mice.Male mice with reduced liver PGC1a expression (LPGC1a) demonstrate greater short-term high-fat/high-sucrose diet-induced weight gain compared to wildtype.Greater positive energy balance during HFHS feeding in male LPGC1a mice is associated with altered food intake patterns and reduced activity energy expenditure.Female LPGC1a mice do not have differences in short-term HFHS-induced body weight gain or energy metabolism compared to wildtype.Disruption of vagal signaling through common hepatic branch vagotomy increases short-term HFHS-induced weight gain in male wildtype mice, but does not alter male LPGC1a weight gain.


Drug Research ◽  
2020 ◽  
Vol 70 (09) ◽  
pp. 410-416
Author(s):  
Leila Etemad ◽  
Hadi Farkhari ◽  
Mohaddeseh Sadat Alavi ◽  
Ali Roohbakhsh

Abstract Objective Dihydromyricetin (DHM), a natural flavonoid, is used to reduce alcohol hangover. It has a modulatory role on GABAA receptors with significant effects on seizure and anxiety in animal models. We aimed to evaluate the effect of DHM on morphine conditioned place preference (CPP) and withdrawal sings following morphine dependence using animal models. Methods The effect of DHM (1, 2 and 5 mg/kg, intraperitoneal; ip) on the acquisition and expression of morphine-induced CPP was evaluated in male mice. Administration of morphine for three consecutive days induced physical dependence. The withdrawal signs such as jumping and defecation were precipitated by administration of naloxone (8 mg/kg, ip). The effect of DHM on the development of physical dependence was assessed by injection of DHM before morphine administrations. Results DHM, at the dose of 5 mg/kg, reduced expression of morphine CPP with an increase in the locomotor activity. DHM, at the doses of 2 and 5 mg/kg, also reduced development of morphine CPP. DHM alleviated development of morphine-induced physical dependence at the dose of 1, 2, and 5 mg/kg by decreasing jumping and defecation. Conclusion These results indicated that DHM decreased acquisition and expression of morphine CPP and inhibited development of morphine-induced physical dependence.


Endocrinology ◽  
2018 ◽  
Vol 159 (9) ◽  
pp. 3158-3176 ◽  
Author(s):  
Juliette Brown ◽  
Andrew Sagante ◽  
Thomas Mayer ◽  
Anna Wright ◽  
Raluca Bugescu ◽  
...  

Abstract The lateral hypothalamic area (LHA) is essential for motivated ingestive and locomotor behaviors that impact body weight, yet it remains unclear how the neurochemically defined subpopulations of LHA neurons contribute to energy balance. In particular, the role of the large population of LHA neurotensin (Nts) neurons has remained ambiguous due to the lack of methods to easily visualize and modulate these neurons. Because LHA Nts neurons are activated by leptin and other anorectic cues and they modulate dopamine or local LHA orexin neurons implicated in energy balance, they may have important, unappreciated roles for coordinating behaviors necessary for proper body weight. In this study, we genetically ablated or chemogenetically inhibited LHA Nts neurons in adult mice to determine their necessity for control of motivated behaviors and body weight. Genetic ablation of LHA Nts neurons resulted in profoundly increased adiposity compared with mice with intact LHA Nts neurons, as well as diminished locomotor activity, energy expenditure, and water intake. Complete loss of LHA Nts neurons also led to downregulation of orexin, revealing important cross-talk between the LHA Nts and orexin populations in maintenance of behavior and body weight. In contrast, chemogenetic inhibition of intact LHA Nts neurons did not disrupt orexin expression, but it suppressed locomotor activity and the adaptive response to leptin. Taken together, these data reveal the necessity of LHA Nts neurons and their activation for controlling energy balance, and that LHA Nts neurons influence behavior and body weight via orexin-dependent and orexin-independent mechanisms.


2010 ◽  
Vol 45 (5) ◽  
pp. 341-353 ◽  
Author(s):  
M W A de Backer ◽  
M A D Brans ◽  
A J van Rozen ◽  
E M van der Zwaal ◽  
M C M Luijendijk ◽  
...  

An increase in brain suppressor of cytokine signaling 3 (SOCS3) has been implicated in the development of both leptin and insulin resistance. Socs3 mRNA is localized throughout the brain, and it remains unclear which brain areas are involved in the effect of SOCS3 levels on energy balance. We investigated the role of SOCS3 expressed in the mediobasal hypothalamus (MBH) in the development of diet-induced obesity in adult rats. Socs3 mRNA was down-regulated by local injection of adeno-associated viral vectors expressing a short hairpin directed against Socs3, after which we determined the response to high-fat high-sucrose choice diet. In contrast to neuronal Socs3 knockout mice, rats with SOCS3 knockdown limited to the MBH showed increased body weight gain, larger amounts of white adipose tissue, and higher leptin concentrations at the end of the experiment. These effects were partly due to the decrease in locomotor activity, as 24 h food intake was comparable with controls. In addition, rats with Socs3 knockdown in the MBH showed alterations in their meal patterns: average meal size in the light period was increased and was accompanied by a compensatory decrease in meal frequency in the dark phase. In addition, neuropeptide Y (Npy) mRNA levels were significantly increased in the arcuate nucleus of Socs3 knockdown rats. Since leptin is known to stimulate Npy transcription in the absence of Socs3, these data suggest that knockdown of Socs3 mRNA limited to the MBH increases Npy mRNA levels, which subsequently decreases locomotor activity and alters feeding patterns.


1999 ◽  
Vol 88 (1) ◽  
pp. 319-328 ◽  
Author(s):  
A. Salvador ◽  
L. Moya-Albiol ◽  
S. Martínez-Sanchis ◽  
V. M. Simón

2017 ◽  
Vol 7 (12) ◽  
Author(s):  
Clara Rossetti ◽  
Daniel Sciarra ◽  
Jean-Marie Petit ◽  
Chin B. Eap ◽  
Olivier Halfon ◽  
...  

Endocrinology ◽  
2003 ◽  
Vol 144 (1) ◽  
pp. 230-239 ◽  
Author(s):  
Sonoko Ogawa ◽  
Johnny Chan ◽  
Jan-Åke Gustafsson ◽  
Kenneth S. Korach ◽  
Donald W. Pfaff

Abstract Estrogens are known to increase running wheel activity of rodents primarily by acting on the medial preoptic area (mPOA). The mechanisms of this estrogenic regulation of running wheel activity are not completely understood. In particular, little is known about the separate roles of two types of estrogen receptors, ERα and ERβ, both of which are expressed in mPOA neurons. In the present study the effects of continuous estrogen treatment on running wheel activity were examined in male and female mice specifically lacking either the ERα (αERKO) or the ERβ (βERKO) gene. Mice were gonadectomized and 1 wk later implanted with either a low dose (16 ng/d) or a high dose (160 ng/d) of estradiol benzoate (EB) or with a placebo control pellet. Home cage running wheel activity was recorded for 9 d starting 10 d after EB implants. The same mice were also tested for open field activity before and after EB implants. In both female and male αERKO mice, running wheel activity was not different from that in corresponding wild-type (αWT) mice in placebo control groups. In both females and males it was increased by EB only in αWT, not αERKO, mice. In βERKO mice, on the other hand, both doses of EB equally increased running wheel activity in both sexes just as they did in βWT mice. Absolute numbers of daily revolutions of EB-treated groups, however, were significantly lower in βERKO females compared with βWT females. Before EB treatment, gonadectomized αERKO female were significantly less active than αWT mice in open field tests, whereas βERKO females tended to be more active than βWT mice. In male mice there were no effect of ERα or ERβ gene knockout on open field activity. Unlike its effect on running wheel activity, EB treatment induced only a small increase in open field activity in female, but not male, mice. These findings indicate that 1) in both sexes estrogenic regulation of running wheel activity is primarily mediated through the ERα, not the ERβ; and 2) hormone/genotype effects are specific to the type of locomotor activity (i.e. home cage running wheel activity and open field activity) measured.


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