scholarly journals POMC-specific knockdown of Tril reduces body adiposity and increases hypothalamic leptin responsiveness

2020 ◽  
Author(s):  
Alexandre Moura-Assis ◽  
Pedro A. Nogueira ◽  
Jose C. de-Lima-Junior ◽  
Fernando M. Simabuco ◽  
Joana M. Gaspar ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Arcuate Nucleus ◽  
Whole Body ◽  
Potential Candidate ◽  
Diet Induced Obesity ◽  
Body Adiposity ◽  
Hypothalamic Inflammation ◽  
Leucine Rich Repeats ◽  
Body Energy ◽  
Harmful Effects

AbstractIn a public dataset of transcripts differentially expressed in selected neuronal subpopulations of the arcuate nucleus, we identified TLR4-interactor with leucine-rich repeats (Tril) as a potential candidate for mediating the harmful effects of a high-fat diet in proopiomelanocortin (POMC) neurons. The non-cell-specific inhibition of Tril in the arcuate nucleus resulted in reduced hypothalamic inflammation, protection against diet-induced obesity associated with increased whole-body energy expenditure and increased systemic glucose tolerance. The inhibition of Tril, specifically in POMC neurons, resulted in a trend for protection against diet-induced obesity, increased energy expenditure and increased hypothalamic sensitivity to leptin. Thus, Tril emerges as a new component of the complex mechanisms that promote hypothalamic dysfunction in experimental diet-induced obesity.

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.

scholarly journals Maternal Transmission of Human OGG1 Protects Mice Against Genetically- and Diet-Induced Obesity Through Increased Tissue Mitochondrial Content

2021 ◽  
Vol 9 ◽  
Author(s):  
Natalie Burchat ◽  
Priyanka Sharma ◽  
Hong Ye ◽  
Sai Santosh Babu Komakula ◽  
Agnieszka Dobrzyn ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Energy Expenditure ◽  
Whole Body ◽  
Chow Diet ◽  
Maternal Transmission ◽  
Mitochondrial Content ◽  
Diet Induced Obesity ◽  
Body Energy ◽  
Obesity Resistance

Obesity and related metabolic disorders are pressing public health concerns, raising the risk for a multitude of chronic diseases. Obesity is multi-factorial disease, with both diet and lifestyle, as well as genetic and developmental factors leading to alterations in energy balance. In this regard, a novel role for DNA repair glycosylases in modulating risk for obesity has been previously established. Global deletion of either of two different glycosylases with varying substrate specificities, Nei-like endonuclease 1 (NEIL1) or 8-oxoguanine DNA glycosylase-1 (OGG1), both predispose mice to diet-induced obesity (DIO). Conversely, enhanced expression of the human OGG1 gene renders mice resistant to obesity and adiposity. This resistance to DIO is mediated through increases in whole body energy expenditure and increased respiration in adipose tissue. Here, we report that hOGG1 expression also confers resistance to genetically-induced obesity. While Agouti obese (Ay/a) mice are hyperphagic and consequently develop obesity on a chow diet, hOGG1 expression in Ay/a mice (Ay/aTg) prevents increased body weight, without reducing food intake. Instead, obesity resistance in Ay/aTg mice is accompanied by increased whole body energy expenditure and tissue mitochondrial content. We also report for the first time that OGG1-mediated obesity resistance in both the Ay/a model and DIO model requires maternal transmission of the hOGG1 transgene. Maternal, but not paternal, transmission of the hOGG1 transgene is associated with obesity resistance and increased mitochondrial content in adipose tissue. These data demonstrate a critical role for OGG1 in modulating energy balance through changes in adipose tissue function. They also demonstrate the importance of OGG1 in modulating developmental programming of mitochondrial content and quality, thereby determining metabolic outcomes in offspring.

scholarly journals Increased whole body energy expenditure and protection against diet-induced obesity in Cyp8b1-deficient mice is accompanied by altered adipose tissue features

Adipocyte ◽  
2020 ◽  
Vol 9 (1) ◽  
pp. 587-599
Author(s):  
Ulrika Axling ◽  
Michele Cavalera ◽  
Eva Degerman ◽  
Mats Gåfvels ◽  
Gösta Eggertsen ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Whole Body ◽  
Diet Induced Obesity ◽  
Body Energy ◽  
Deficient Mice

Intraduodenal infusion of α-ketoglutarate decreases whole body energy expenditure in growing pigs

2006 ◽  
Vol 25 (3) ◽  
pp. 489-496 ◽  
Author(s):  
Peter Junghans ◽  
Michael Derno ◽  
Stefan Pierzynowski ◽  
Ulf Hennig ◽  
Paul Eberhard Rudolph ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Growing Pigs ◽  
Whole Body ◽  
Intraduodenal Infusion ◽  
Body Energy

scholarly journals A combination of exercise and capsinoid supplementation additively suppresses diet-induced obesity by increasing energy expenditure in mice

2015 ◽  
Vol 308 (4) ◽  
pp. E315-E323 ◽  
Author(s):  
Kana Ohyama ◽  
Yoshihito Nogusa ◽  
Katsuya Suzuki ◽  
Kosaku Shinoda ◽  
Shingo Kajimura ◽  
...  
Keyword(s):  
Skeletal Muscle ◽  
Body Weight ◽  
Adipose Tissue ◽  
Weight Gain ◽  
Energy Expenditure ◽  
Body Weight Gain ◽  
Whole Body ◽  
Voluntary Running ◽  
Running Wheel Exercise ◽  
Body Energy

Exercise effectively prevents the development of obesity and obesity-related diseases such as type 2 diabetes. Capsinoids (CSNs) are capsaicin analogs found in a nonpungent pepper that increase whole body energy expenditure. Although both exercise and CSNs have antiobesity functions, the effectiveness of exercise with CSN supplementation has not yet been investigated. Here, we examined whether the beneficial effects of exercise could be further enhanced by CSN supplementation in mice. Mice were randomly assigned to four groups: 1) high-fat diet (HFD, Control), 2) HFD containing 0.3% CSNs, 3) HFD with voluntary running wheel exercise (Exercise), and 4) HFD containing 0.3% CSNs with voluntary running wheel exercise (Exercise + CSN). After 8 wk of ingestion, blood and tissues were collected and analyzed. Although CSNs significantly suppressed body weight gain under the HFD, CSN supplementation with exercise additively decreased body weight gain and fat accumulation and increased whole body energy expenditure compared with exercise alone. Exercise together with CSN supplementation robustly improved metabolic profiles, including the plasma cholesterol level. Furthermore, this combination significantly prevented diet-induced liver steatosis and decreased the size of adipocyte cells in white adipose tissue. Exercise and CSNs significantly increased cAMP levels and PKA activity in brown adipose tissue (BAT), indicating an increase of lipolysis. Moreover, they significantly activated both the oxidative phosphorylation gene program and fatty acid oxidation in skeletal muscle. These results indicate that CSNs efficiently promote the antiobesity effect of exercise, in part by increasing energy expenditure via the activation of fat oxidation in skeletal muscle and lipolysis in BAT.

scholarly journals Daily Ingestion of Grains of Paradise (Aframomum melegueta) Extract Increases Whole-Body Energy Expenditure and Decreases Visceral Fat in Humans

2014 ◽  
Vol 60 (1) ◽  
pp. 22-27 ◽  
Author(s):  
Jun SUGITA ◽  
Takeshi YONESHIRO ◽  
Yuuki SUGISHIMA ◽  
Takeshi IKEMOTO ◽  
Hideyo UCHIWA ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Visceral Fat ◽  
Whole Body ◽  
Daily Ingestion ◽  
Body Energy

scholarly journals Hypothalamic stearoyl-CoA desaturase-2 (SCD2) controls whole-body energy expenditure

2015 ◽  
Vol 40 (3) ◽  
pp. 471-478 ◽  
Author(s):  
R F de Moura ◽  
L F Nascimento ◽  
L M Ignacio-Souza ◽  
J Morari ◽  
D S Razolli ◽  
...  
Keyword(s):  
Energy Expenditure ◽  
Whole Body ◽  
Stearoyl Coa Desaturase ◽  
Body Energy

scholarly journals Hepatocyte-specific Hepatocyte Nuclear Factor 4 alpha (HNF4) deletion decreases resting energy expenditure by disrupting lipid and carbohydrate homeostasis

2021 ◽  
Author(s):  
Ian Huck ◽  
E. Matthew Morris ◽  
John Thyfault ◽  
Udayan Apte
Keyword(s):  
Energy Expenditure ◽  
Energy Homeostasis ◽  
Energy Utilization ◽  
Lipid Absorption ◽  
Whole Body ◽  
Positive Energy ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Hepatocyte Nuclear Factor 4 ◽  
Body Energy

Hepatocyte Nuclear Factor 4 alpha (HNF4α) is required for hepatocyte differentiation and regulates expression of genes involved in lipid and carbohydrate metabolism including those that control VLDL secretion and gluconeogenesis. Whereas previous studies have focused on specific genes regulated by HNF4α in metabolism, its overall role in whole body energy utilization has not been studied. In this study, we used indirect calorimetry to determine the effect of hepatocyte-specific HNF4α deletion (HNF4α-KO) in mice on whole body energy expenditure (EE) and substrate utilization in fed, fasted, and high fat diet (HFD) conditions. HNF4α-KO had reduced resting EE during fed conditions and higher rates of carbohydrate oxidation with fasting. HNF4α-KO mice exhibited decreased body mass caused by fat mass depletion despite no change in energy intake and evidence of positive energy balance. HNF4α-KO mice were able to upregulate lipid oxidation during HFD suggesting that their metabolic flexibility was intact. However, only hepatocyte specific HNF4α-KO mice exhibited significant reduction in basal metabolic rate and spontaneous activity during HFD. Consistent with previous studies, hepatic gene expression in HNF4α-KO supports decreased gluconeogenesis and decreased VLDL export and hepatic Beta-oxidation in HNF4α-KO livers across all feeding conditions. Together, our data suggest deletion of hepatic HNF4α increases dependence on dietary carbohydrates and endogenous lipids for energy during fed and fasted conditions by inhibiting hepatic gluconeogenesis, hepatic lipid export, and intestinal lipid absorption resulting in decreased whole body energy expenditure. These data clarify the role of hepatic HNF4α on systemic metabolism and energy homeostasis.

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