Adipocyte‐Specific Ablation of Long‐Chain Acyl‐CoA Synthetase‐4 (ACSL4) in Mice Protects Against Diet‐Induced Obesity‐Associated Decreases in White Adipocyte Oxygen Consumption and Whole Body Energy Expenditure

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.

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

10.1101/2020.06.25.172379 ◽

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.

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

Adipocyte ◽

10.1080/21623945.2020.1827519 ◽

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

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Long-chain acyl-CoA esters as indicators of lipid metabolism and insulin sensitivity in rat and human muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.2000.279.3.e554 ◽

2000 ◽

Vol 279 (3) ◽

pp. E554-E560 ◽

Cited By ~ 146

Author(s):

Bronwyn A. Ellis ◽

Ann Poynten ◽

Andrew J. Lowy ◽

Stuart M. Furler ◽

Donald J. Chisholm ◽

...

Keyword(s):

Adipose Tissue ◽

Lipid Metabolism ◽

Insulin Action ◽

Human Muscle ◽

Whole Body ◽

Cellular Processes ◽

Lipid Species ◽

Chain Acyl ◽

Triglyceride Content ◽

Long Chain

Long-chain acyl-CoAs (LCACoA) are an activated lipid species that are key metabolites in lipid metabolism; they also have a role in the regulation of other cellular processes. However, few studies have linked LCACoA content in rat and human muscle to changes in nutritional status and insulin action. Fasting rats for 18 h significantly elevated the three major LCACoA species in muscle ( P < 0.001), whereas high-fat feeding of rats with a safflower oil (18:2) diet produced insulin resistance and increased total LCACoA content ( P < 0.0001) by specifically increasing 18:2-CoA. The LCACoA content of red muscle from rats (4–8 nmol/g) was 4- to 10-fold higher than adipose tissue (0.4–0.9 nmol/g, P < 0.001), suggesting that any contamination of muscle samples with adipocytes would contribute little to the LCACoA content of muscle. In humans, the LCACoA content of muscle correlated significantly with a measure of whole body insulin action in 17 male subjects ( r 2 = 0.34, P = 0.01), supporting a link between muscle lipid metabolism and insulin action. These results demonstrate that the LCACoA pool reflects lipid metabolism and nutritional state in muscle. We conclude that the LCACoA content of muscle provides a direct index of intracellular lipid metabolism and its links to insulin action, which, unlike triglyceride content, is not subject to contamination by closely associated adipose tissue.

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

Scientific Reports ◽

10.1038/s41598-021-97291-7 ◽

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.

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

Clinical Nutrition ◽

10.1016/j.clnu.2005.11.003 ◽

2006 ◽

Vol 25 (3) ◽

pp. 489-496 ◽

Cited By ~ 28

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

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Resistance to High-fat Diet-Induced Obesity and Insulin Resistance in Mice with Very Long-Chain Acyl-CoA Dehydrogenase Deficiency

Cell Metabolism ◽

10.1016/j.cmet.2010.06.004 ◽

2010 ◽

Vol 12 (1) ◽

pp. 103

Author(s):

Dongyan Zhang ◽

Jennifer Christianson ◽

Zhen-Xiang Liu ◽

Liqun Tian ◽

Cheol Soo Choi ◽

...

Keyword(s):

Insulin Resistance ◽

High Fat Diet ◽

Dehydrogenase Deficiency ◽

High Fat ◽

Diet Induced Obesity ◽

Chain Acyl ◽

Long Chain

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Mathematical Model for the Contribution of Individual Organs to Non-Zero Y-Intercepts in Single and Multi-Compartment Linear Models of Whole-Body Energy Expenditure

PLoS ONE ◽

10.1371/journal.pone.0103301 ◽

2014 ◽

Vol 9 (7) ◽

pp. e103301 ◽

Cited By ~ 11

Author(s):

Karl J. Kaiyala

Keyword(s):

Mathematical Model ◽

Energy Expenditure ◽

Linear Models ◽

Whole Body ◽

Body Energy

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

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00354.2014 ◽

2015 ◽

Vol 308 (4) ◽

pp. E315-E323 ◽

Cited By ~ 37

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.

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