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

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 The transcription factor hepatocyte nuclear factor 4A acts in the intestine to promote white adipose tissue energy storage

2022 ◽  
Vol 13 (1) ◽  
Author(s):  
Romain Girard ◽  
Sarah Tremblay ◽  
Christophe Noll ◽  
Stéphanie St-Jean ◽  
Christine Jones ◽  
...  
Keyword(s):  
Transcription Factor ◽  
Adipose Tissue ◽  
Lipid Metabolism ◽  
White Adipose Tissue ◽  
Whole Body ◽  
Nuclear Factor ◽  
Hepatocyte Nuclear Factor ◽  
Diet Induced Obesity ◽  
Regulatory Circuit ◽  
Body Energy

AbstractThe transcription factor hepatocyte nuclear factor 4 A (HNF4A) controls the metabolic features of several endodermal epithelia. Both HNF4A and HNF4G are redundant in the intestine and it remains unclear whether HNF4A alone controls intestinal lipid metabolism. Here we show that intestinal HNF4A is not required for intestinal lipid metabolism per se, but unexpectedly influences whole-body energy expenditure in diet-induced obesity (DIO). Deletion of intestinal HNF4A caused mice to become DIO-resistant with a preference for fat as an energy substrate and energetic changes in association with white adipose tissue (WAT) beiging. Intestinal HNF4A is crucial for the fat-induced release of glucose-dependent insulinotropic polypeptide (GIP), while the reintroduction of a stabilized GIP analog rescues the DIO resistance phenotype of the mutant mice. Our study provides evidence that intestinal HNF4A plays a non-redundant role in whole-body lipid homeostasis and points to a non-cell-autonomous regulatory circuit for body-fat management.

scholarly journals Disruption of the sugar-sensing receptor T1R2 attenuates metabolic derangements associated with diet-induced obesity

2016 ◽  
Vol 310 (8) ◽  
pp. E688-E698 ◽  
Author(s):  
Kathleen R. Smith ◽  
Tania Hussain ◽  
Elnaz Karimian Azari ◽  
Jennifer L. Steiner ◽  
Julio E. Ayala ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Balance ◽  
Fat Mass ◽  
Glucose Homeostasis ◽  
Sweet Taste ◽  
Nutrient Sensing ◽  
Whole Body ◽  
Receptor Protein ◽  
Peripheral Tissues ◽  
Diet Induced Obesity

Sweet taste receptors (STRs) on the tongue mediate gustatory sweet sensing, but their expression in the gut, pancreas, and adipose tissue suggests a physiological contribution to whole body nutrient sensing and metabolism. However, little is known about the function and contribution of these sugar sensors during metabolic stress induced by overnutrition and subsequent obesity. Here, we investigated the effects of high-fat/low-carbohydrate (HF/LC) diet on glucose homeostasis and energy balance in mice with global disruption of the sweet taste receptor protein T1R2. We assessed body composition, energy balance, glucose homeostasis, and tissue-specific nutrient metabolism in T1R2 knockout (T1R2-KO) mice fed a HF/LC diet for 12 wk. HF/LC diet-fed T1R2-KO mice gained a similar amount of body mass as did WT mice, but had reduced fat mass and increased lean mass relative to WT mice. T1R2-KO mice were also hyperphagic and hyperactive. Ablation of the T1R2 sugar sensor protected mice from HF/LC diet-induced hyperinsulinemia and altered substrate utilization, including increased rates of glucose oxidation and decreased liver triglyceride (TG) accumulation, despite normal intestinal fat absorption. Finally, STRs ( T1r2/T1r3) were upregulated in the adipose tissue of WT mice in response to HF/LC diet, and their expression positively correlated with fat mass and glucose intolerance. The chemosensory receptor T1R2, plays an important role in glucose homeostasis during diet-induced obesity through the regulation of yet to be identified molecular mechanisms that alter energy disposal and utilization in peripheral tissues.

scholarly journals Grains of paradise (Aframomum melegueta) extract activates brown adipose tissue and increases whole-body energy expenditure in men

2013 ◽  
Vol 110 (4) ◽  
pp. 733-738 ◽  
Author(s):  
Jun Sugita ◽  
Takeshi Yoneshiro ◽  
Takuya Hatano ◽  
Sayuri Aita ◽  
Takeshi Ikemoto ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Human Subjects ◽  
Whole Body ◽  
Negative Group ◽  
Oral Ingestion ◽  
Positive Group ◽  
Bat Activity ◽  
Brown Adipose ◽  
Body Energy

Brown adipose tissue (BAT) is responsible for cold- and diet-induced thermogenesis, and thereby contributes to the control of whole-body energy expenditure (EE) and body fat content. BAT activity can be assessed by fluoro-2-deoxyglucose (FDG)-positron emission tomography (PET) in human subjects. Grains of paradise (GP, Aframomum melegueta), a species of the ginger family, contain pungent, aromatic ketones such as 6-paradol, 6-gingerol and 6-shogaol. An alcohol extract of GP seeds and 6-paradol are known to activate BAT thermogenesis in small rodents. The present study aimed to examine the effects of the GP extract on whole-body EE and to analyse its relation to BAT activity in men. A total of nineteen healthy male volunteers aged 20–32 years underwent FDG-PET after 2 h of exposure to cold at 19°C with light clothing. A total of twelve subjects showed marked FDG uptake into the adipose tissue of the supraclavicular and paraspinal regions (BAT positive). The remaining seven showed no detectable uptake (BAT negative). Within 4 weeks after the FDG-PET examination, whole-body EE was measured at 27°C before and after oral ingestion of GP extract (40 mg) in a single-blind, randomised, placebo-controlled, crossover design. The resting EE of the BAT-positive group did not differ from that of the BAT-negative group. After GP extract ingestion, the EE of the BAT-positive group increased within 2 h to a significantly greater (P< 0·01) level than that of the BAT-negative group. Placebo ingestion produced no significant change in EE. These results suggest that oral ingestion of GP extract increases whole-body EE through the activation of BAT in human subjects.

scholarly journals Brown Adipose Tissue, Whole-Body Energy Expenditure, and Thermogenesis in Healthy Adult Men

Obesity ◽  
2011 ◽  
Vol 19 (1) ◽  
pp. 13-16 ◽  
Author(s):  
Takeshi Yoneshiro ◽  
Sayuri Aita ◽  
Mami Matsushita ◽  
Toshimitsu Kameya ◽  
Kunihiro Nakada ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Brown Adipose Tissue ◽  
Healthy Adult ◽  
Whole Body ◽  
Adult Men ◽  
Brown Adipose ◽  
Body Energy

scholarly journals Mitochondrial uncoupling in skeletal muscle by UCP1 augments energy expenditure and glutathione content while mitigating ROS production

2013 ◽  
Vol 305 (3) ◽  
pp. E405-E415 ◽  
Author(s):  
Cyril Nii-Klu Adjeitey ◽  
Ryan J. Mailloux ◽  
Robert A. deKemp ◽  
Mary-Ellen Harper
Keyword(s):  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Energy Expenditure ◽  
Whole Body ◽  
Proton Leak ◽  
Muscle Mitochondria ◽  
Mitochondrial Ros ◽  
Bat Mitochondria ◽  
Ucp1 Expression ◽  
Body Energy

Enhancement of proton leaks in muscle tissue represents a potential target for obesity treatment. In this study, we examined the bioenergetic and physiological implications of increased proton leak in skeletal muscle. To induce muscle-specific increases in proton leak, we used mice that selectively express uncoupling protein-1 (UCP1) in skeletal muscle tissue. UCP1 expression in muscle mitochondria was ∼13% of levels in brown adipose tissue (BAT) mitochondria and caused increased GDP-sensitive proton leak. This was associated with an increase in whole body energy expenditure and a decrease in white adipose tissue content. Muscle UCP1 activity had divergent effects on mitochondrial ROS emission and glutathione levels compared with BAT. UCP1 in muscle increased total mitochondrial glutathione levels ∼7.6 fold. Intriguingly, unlike in BAT mitochondria, leak through UCP1 in muscle controlled mitochondrial ROS emission. Inhibition of UCP1 with GDP in muscle mitochondria increased ROS emission ∼2.8-fold relative to WT muscle mitochondria. GDP had no impact on ROS emission from BAT mitochondria from either genotype. Collectively, these findings indicate that selective induction of UCP1-mediated proton leak in muscle can increase whole body energy expenditure and decrease adiposity. Moreover, ectopic UCP1 expression in skeletal muscle can control mitochondrial ROS emission, while it apparently plays no such role in its endogenous tissue, brown fat.

Adipocyte-specific mTORC2 deficiency impairs BAT and iWAT thermogenic capacity without affecting glucose uptake and energy expenditure in cold-acclimated mice

2021 ◽  
Author(s):  
Erique Castro ◽  
Thayna S Vieira ◽  
Tiago E. Oliveira ◽  
Milene Ortiz-Silva ◽  
Maynara L Andrade ◽  
...  
Keyword(s):  
Adipose Tissue ◽  
Energy Expenditure ◽  
Glucose Uptake ◽  
Residual Activity ◽  
De Novo Lipogenesis ◽  
Whole Body ◽  
Mrna Levels ◽  
Brown Adipose ◽  
Body Energy ◽  
Thermogenic Capacity

Deletion of mTORC2 essential component Rictor by a Cre recombinase under control of the broad, non-adipocyte specific aP2/FABP4 promoter impairs thermoregulation and brown adipose tissue (BAT) glucose uptake upon acute cold exposure. We investigated herein whether adipocyte-specific mTORC2 deficiency affects BAT and inguinal white adipose tissue (iWAT) signaling, metabolism and thermogenesis in cold-acclimated mice. For this, 8-weeks old male mice bearing Rictor deletion and therefore mTORC2 deficiency in adipocytes (adiponectin-Cre) and littermates controls were either kept at thermoneutrality (30 ± 1ºC) or cold-acclimated (10 ± 1ºC) for 14 days and evaluated for BAT and iWAT signaling, metabolism and thermogenesis. Cold acclimation inhibited mTORC2 in BAT and iWAT, but its residual activity is still required for the cold-induced increases in BAT adipocyte number, total UCP-1 content and mRNA levels of proliferation markers Ki67 and cyclin 1D and de novo lipogenesis enzymes ATP-citrate lyase and acetyl-CoA carboxylase. In iWAT, mTORC2 residual activity is partially required for the cold-induced increases in multilocular adipocytes, mitochondrial mass and UCP-1 content. Conversely, BAT mTORC1 activity and BAT and iWAT glucose uptake were upregulated by cold independently of mTORC2. Noteworthy, the impairment in BAT and iWAT total UCP-1 content and thermogenic capacity induced by adipocyte mTORC2 deficiency had no major impact on whole-body energy expenditure in cold-acclimated mice due to a compensatory activation of muscle shivering. In conclusion, adipocyte mTORC2 deficiency impairs, through different mechanisms, BAT and iWAT total UCP-1 content and thermogenic capacity in cold-acclimated mice, without affecting glucose uptake and whole-body energy expenditure.

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.

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