scholarly journals Interplay between diet-induced obesity and chronic stress in mice: potential role of FKBP51

2014 ◽  
Vol 222 (1) ◽  
pp. 15-26 ◽  
Author(s):  
Georgia Balsevich ◽  
Andres Uribe ◽  
Klaus V Wagner ◽  
Jakob Hartmann ◽  
Sara Santarelli ◽  
...  
Keyword(s):  
Chronic Stress ◽  
High Fat Diet ◽  
Metabolic Regulation ◽  
Potential Role ◽  
Body Weight Gain ◽  
Fk506 Binding Protein ◽  
Diet Induced Obesity ◽  
Chronic Social Defeat Stress ◽  
Novel Target

While it is known that stress promotes obesity, the effects of stress within an obesogenic context are not so clear and molecular targets at the interface remain elusive. The FK506-binding protein 51 (FKBP51, gene:Fkbp5) has been identified as a target gene implicated in the development of stress-related psychiatric disorders and is a possible candidate for involvement in stress and metabolic regulation. The aims of the current study are to investigate the interaction between chronic stress and an obesogenic context and to additionally examine whether FKBP51 is involved in this interaction. For this purpose, male C57BL/6 mice were exposed to a high-fat diet for 8 weeks before being challenged with chronic social defeat stress. Herein, we demonstrate that chronic stress induces hypophagia and weight loss, ultimately improving features arising from an obesogenic context, including glucose tolerance and levels of insulin and leptin. We show thatFkbp5expression is responsive to diet and stress in the hypothalamus and hippocampus respectively. Furthermore, under basal conditions, higher levels of hypothalamicFkbp5expression were related to increased body weight gain. Our data indicate thatFkbp5may represent a novel target in metabolic regulation.

scholarly journals Potential Role of Central Microglia Activation in High Fat Diet‐Induced Obesity

2018 ◽  
Vol 32 (S1) ◽  
Author(s):  
Aneesh Singal ◽  
Caitlin R. Coker ◽  
Sarah S. Bingaman ◽  
Amy C. Arnold ◽  
Yuval Silberman
Keyword(s):  
High Fat Diet ◽  
Potential Role ◽  
Microglia Activation ◽  
High Fat ◽  
Diet Induced Obesity

scholarly journals Expression of Melanin-Concentrating Hormone Receptor 2 Protects Against Diet-Induced Obesity in Male Mice

Endocrinology ◽  
2014 ◽  
Vol 155 (1) ◽  
pp. 81-88 ◽  
Author(s):  
Melissa J. S. Chee ◽  
Pavlos Pissios ◽  
Deepthi Prasad ◽  
Eleftheria Maratos-Flier
Keyword(s):  
Energy Balance ◽  
High Fat Diet ◽  
Potential Role ◽  
Early Gene ◽  
Wild Type ◽  
Diet Induced Obesity ◽  
Melanin Concentrating Hormone ◽  
The Central Nervous System ◽  
Insight Into

Melanin-concentrating hormone (MCH) is an orexigenic neuropeptide that is a ligand for two subtypes of MCH receptors, MCHR1 and MCHR2. MCHR1 is universally expressed in mammals ranging from rodents to humans, but the expression of MCHR2 is substantially restricted. In mammals, MCHR2 has been defined in primates as well as other species such as cats and dogs but is not seen in rodents. Although the role of MCHR1 in mediating the actions of MCH on energy balance is clearly defined using mouse models, the role of MCHR2 is harder to characterize because of its limited expression. To determine any potential role of MCHR2 in energy balance, we generated a transgenic MCHR1R2 mouse model, where human MCHR2 is coexpressed in MCHR1-expressing neurons. As shown previously, control wild-type mice expressing only native MCHR1 developed diet-induced obesity when fed a high-fat diet. In contrast, MCHR1R2 mice had lower food intake, leading to their resistance to diet-induced obesity. Furthermore, we showed that MCH action is altered in MCHR1R2 mice. MCH treatment in wild-type mice inhibited the activation of the immediate-early gene c-fos, and coexpression of MCHR2 reduced the inhibitory actions of MCHR1 on this pathway. In conclusion, we developed an experimental animal model that can provide insight into the action of MCHR2 in the central nervous system and suggest that some actions of MCHR2 oppose the endogenous actions of MCHR1.

scholarly journals Activation of mitochondrial TUFM ameliorates metabolic dysregulation through coordinating autophagy induction

2021 ◽  
Vol 4 (1) ◽  
Author(s):  
Dasol Kim ◽  
Hui-Yun Hwang ◽  
Eun Sun Ji ◽  
Jin Young Kim ◽  
Jong Shin Yoo ◽  
...  
Keyword(s):  
Metabolic Regulation ◽  
Elongation Factor ◽  
Dependent Manner ◽  
Diet Induced Obesity ◽  
Metabolic Dysregulation ◽  
Autophagy Induction ◽  
Transcription Factor Eb ◽  
Mitochondrial Elongation

AbstractDisorders of autophagy, a key regulator of cellular homeostasis, cause a number of human diseases. Due to the role of autophagy in metabolic dysregulation, there is a need to identify autophagy regulators as therapeutic targets. To address this need, we conducted an autophagy phenotype-based screen and identified the natural compound kaempferide (Kaem) as an autophagy enhancer. Kaem promoted autophagy through translocation of transcription factor EB (TFEB) without MTOR perturbation, suggesting it is safe for administration. Moreover, Kaem accelerated lipid droplet degradation in a lysosomal activity-dependent manner in vitro and ameliorated metabolic dysregulation in a diet-induced obesity mouse model. To elucidate the mechanism underlying Kaem’s biological activity, the target protein was identified via combined drug affinity responsive target stability and LC–MS/MS analyses. Kaem directly interacted with the mitochondrial elongation factor TUFM, and TUFM absence reversed Kaem-induced autophagy and lipid degradation. Kaem also induced mitochondrial reactive oxygen species (mtROS) to sequentially promote lysosomal Ca2+ efflux, TFEB translocation and autophagy induction, suggesting a role of TUFM in mtROS regulation. Collectively, these results demonstrate that Kaem is a potential therapeutic candidate/chemical tool for treating metabolic dysregulation and reveal a role for TUFM in autophagy for metabolic regulation with lipid overload.

The Potential Role of Neuropeptide Y Expression in the Dorsomedial Hypothalamus in Thermoregulation during Lactation and Diet-Induced Obesity

2011 ◽  
pp. P2-431-P2-431
Author(s):  
Shin J Draper ◽  
Alberto Loche ◽  
Chris J Madden ◽  
Susan Smith ◽  
Shaun F Morrison ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Potential Role ◽  
Dorsomedial Hypothalamus ◽  
Diet Induced Obesity

scholarly journals Nicotinamide Nucleotide Transhydrogenase (Nnt) is Related to Obesity in Mice

2020 ◽  
Vol 52 (12) ◽  
pp. 877-881
Author(s):  
Anne Kunath ◽  
John T. Heiker ◽  
Matthias Kern ◽  
Joanna Kosacka ◽  
Gesine Flehmig ◽  
...  
Keyword(s):  
Fat Mass ◽  
Metabolic Diseases ◽  
Body Weight Gain ◽  
Wild Type ◽  
Inner Mitochondrial Membrane ◽  
Nicotinamide Nucleotide Transhydrogenase ◽  
Diet Induced Obesity ◽  
Highly Sensitive ◽  
Obesity In Mice

AbstractThe C57BL/6J (B6J) mouse strain has been widely used as a control strain for the study of metabolic diseases and diet induced obesity (DIO). B6J mice carry a spontaneous deletion mutation in the nicotinamide nucleotide transhydrogenase (Nnt) gene eliminating exons 7–11, resulting in expression of a truncated form of Nnt, an enzyme that pumps protons across the inner mitochondrial membrane. It has been proposed that this mutation in B6J mice is associated with epigonadal fat mass and altered sensitivity to diet induced obesity. To define the role of Nnt in the development of diet induced obesity, we generated first backcross (BC1) hybrids of wild type Nnt C57BL/6NTac and mutated Nnt C57BL/6JRj [(C57BL/6NTac×C57BL/6JRj)F1×C57BL/6NTac]. Body weight gain and specific fat-pad depot mass were measured in BC1 hybrids under high fat diet conditions. Both sexes of BC1 hybrids indicate that mice with Nnt wild type allele are highly sensitive to DIO and exhibit higher relative fat mass. In summary, our data indicate that the Nnt mutation in mice is associated with sensitivity to DIO and fat mass.

scholarly journals TLR4-interactor with leucine-rich repeats (TRIL) is involved in diet-induced hypothalamic inflammation

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Alexandre Moura-Assis ◽  
Pedro A. S. Nogueira ◽  
Jose C. de-Lima-Junior ◽  
Fernando M. Simabuco ◽  
Joana M. Gaspar ◽  
...  
Keyword(s):  
Dietary Fats ◽  
Whole Body ◽  
Metabolic Dysfunction ◽  
Diet Induced Obesity ◽  
Hypothalamic Inflammation ◽  
Novel Target ◽  
Tlr4 Activation ◽  
Leucine Rich Repeats ◽  
Body Energy

AbstractObesity and high-fat diet (HFD) consumption result in hypothalamic inflammation and metabolic dysfunction. While the TLR4 activation by dietary fats is a well-characterized pathway involved in the neuronal and glial inflammation, the role of its accessory proteins in diet-induced hypothalamic inflammation remains unknown. Here, we demonstrate that the knockdown of TLR4-interactor with leucine-rich repeats (Tril), a functional component of TLR4, resulted in reduced hypothalamic inflammation, increased whole-body energy expenditure, improved the systemic glucose tolerance and protection from diet-induced obesity. The POMC-specific knockdown of Tril resulted in decreased body fat, decreased white adipose tissue inflammation and a trend toward increased leptin signaling in POMC neurons. Thus, Tril was identified as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental obesity and its inhibition in the hypothalamus may represent a novel target for obesity treatment.

Ameliorative effect of selegiline in high fat diet induced obesity rat model: Possible role of dopaminergic pathway

2020 ◽  
Vol 20 ◽  
pp. 100301
Author(s):  
Amit Goyal ◽  
Ankita Sharma ◽  
Deepika Sharma ◽  
Tapan Behl ◽  
Anjoo Kamboj ◽  
...  
Keyword(s):  
Rat Model ◽  
High Fat Diet ◽  
High Fat ◽  
Diet Induced Obesity ◽  
Dopaminergic Pathway ◽  
Ameliorative Effect
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