scholarly journals Directing visceral white adipocyte precursors to a thermogenic adipocyte fate improves insulin sensitivity in obese mice

eLife ◽  
2017 ◽  
Vol 6 ◽  
Author(s):  
Chelsea Hepler ◽  
Mengle Shao ◽  
Jonathan Y Xia ◽  
Alexandra L Ghaben ◽  
Mackenzie J Pearson ◽  
...  

Visceral adiposity confers significant risk for developing metabolic disease in obesity whereas preferential expansion of subcutaneous white adipose tissue (WAT) appears protective. Unlike subcutaneous WAT, visceral WAT is resistant to adopting a protective thermogenic phenotype characterized by the accumulation of Ucp1+ beige/BRITE adipocytes (termed ‘browning’). In this study, we investigated the physiological consequences of browning murine visceral WAT by selective genetic ablation of Zfp423, a transcriptional suppressor of the adipocyte thermogenic program. Zfp423 deletion in fetal visceral adipose precursors (Zfp423loxP/loxP; Wt1-Cre), or adult visceral white adipose precursors (PdgfrbrtTA; TRE-Cre; Zfp423loxP/loxP), results in the accumulation of beige-like thermogenic adipocytes within multiple visceral adipose depots. Thermogenic visceral WAT improves cold tolerance and prevents and reverses insulin resistance in obesity. These data indicate that beneficial visceral WAT browning can be engineered by directing visceral white adipocyte precursors to a thermogenic adipocyte fate, and suggest a novel strategy to combat insulin resistance in obesity.

Antioxidants ◽  
2019 ◽  
Vol 8 (9) ◽  
pp. 360 ◽  
Author(s):  
Viviana Sandoval ◽  
Antoni Femenias ◽  
Úrsula Martínez-Garza ◽  
Hèctor Sanz-Lamora ◽  
Juan Castagnini ◽  
...  

Maqui (Aristotelia Chilensis) berry features a unique profile of anthocyanidins that includes high amounts of delphinidin-3-O-sambubioside-5-O-glucoside and delphinidin-3-O-sambubioside and has shown positive effects on fasting glucose and insulin levels in humans and murine models of type 2 diabetes and obesity. The molecular mechanisms underlying the impact of maqui on the onset and development of the obese phenotype and insulin resistance was investigated in high fat diet-induced obese mice supplemented with a lyophilized maqui berry. Maqui-dietary supplemented animals showed better insulin response and decreased weight gain but also a differential expression of genes involved in de novo lipogenesis, fatty acid oxidation, multilocular lipid droplet formation and thermogenesis in subcutaneous white adipose tissue (scWAT). These changes correlated with an increased expression of the carbohydrate response element binding protein b (Chrebpb), the sterol regulatory binding protein 1c (Srebp1c) and Cellular repressor of adenovirus early region 1A–stimulated genes 1 (Creg1) and an improvement in the fibroblast growth factor 21 (FGF21) signaling. Our evidence suggests that maqui dietary supplementation activates the induction of fuel storage and thermogenesis characteristic of a brown-like phenotype in scWAT and counteracts the unhealthy metabolic impact of an HFD. This induction constitutes a putative strategy to prevent/treat diet-induced obesity and its associated comorbidities.


Life Sciences ◽  
2021 ◽  
Vol 278 ◽  
pp. 119562
Author(s):  
Guangzhen He ◽  
Jiaowei Gu ◽  
Huawei Wang ◽  
Siyuan Cheng ◽  
Qing Xiong ◽  
...  

Obesity ◽  
2012 ◽  
Author(s):  
Gong-Rak Lee ◽  
Mi Kyung Shin ◽  
Dong-Joon Yoon ◽  
Ah-Ram Kim ◽  
Rina Yu ◽  
...  

Diabetes ◽  
2018 ◽  
Vol 67 (Supplement 1) ◽  
pp. 1850-P
Author(s):  
CHEN WANG ◽  
KAIDA MU ◽  
TIANXUE ZHAO ◽  
HUI ZHU ◽  
WEIPING JIA

Diabetes ◽  
2019 ◽  
Vol 68 (Supplement 1) ◽  
pp. 1944-P
Author(s):  
DAVID A. CAPPEL ◽  
AMBRA POZZI ◽  
ROY ZENT ◽  
DAVID WASSERMAN

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Daniel Andersen ◽  
Henrik Munch Roager ◽  
Li Zhang ◽  
Janne Marie Moll ◽  
Henrik Lauritz Frandsen ◽  
...  

AbstractWhile prolonged fasting induces significant metabolic changes in humans and mice, less is known about systems-wide metabolic changes in response to short-term feed deprivation, which is used in experimental animal studies prior to metabolic challenge tests. We here performed a systems biology-based investigation of connections between gut bacterial composition and function, inflammatory and metabolic parameters in the intestine, liver, visceral adipose tissue, blood and urine in high-fat fed, obese mice that were feed deprived up to 12 h. The systems-wide analysis revealed that feed deprivation linked to enhanced intestinal butyric acid production and expression of the gene encoding the pro-thermogenic uncoupling protein UCP1 in visceral adipose tissue of obese mice. Ucp1 expression was also positively associated with Il33 expression in ileum, colon and adipose tissue as well as with the abundance of colonic Porphyromonadaceae, the latter also correlating to cecal butyric acid levels. Collectively, the data highlighted presence of a multi-tiered system of inter-tissue communication involving intestinal, immune and metabolic functions which is affected by feed deprivation in obese mice, thus pointing to careful use of short-feed deprivation in metabolic studies using obese mice.


Author(s):  
Jana Jurkovičová ◽  
Katarína Hirošová ◽  
Diana Vondrová ◽  
Martin Samohýl ◽  
Zuzana Štefániková ◽  
...  

The prevalence of cardiometabolic risk factors has increased in Slovakian adolescents as a result of serious lifestyle changes. This cross-sectional study aimed to assess the prevalence of insulin resistance (IR) and the associations with cardiometabolic and selected lifestyle risk factors in a sample of Slovak adolescents. In total, 2629 adolescents (45.8% males) aged between 14 and 18 years were examined in the study. Anthropometric parameters, blood pressure (BP), and resting heart rate were measured; fasting venous blood samples were analyzed; and homeostasis model assessment (HOMA)-insulin resistance (IR) was calculated. For statistical data processing, the methods of descriptive and analytical statistics for normal and skewed distribution of variables were used. The mean HOMA-IR was 2.45 ± 1.91, without a significant sex differences. IR (cut-off point for HOMA-IR = 3.16) was detected in 18.6% of adolescents (19.8% males, 17.6% females). IR was strongly associated with overweight/obesity (especially central) and with almost all monitored cardiometabolic factors, except for total cholesterol (TC) and systolic BP in females. The multivariate model selected variables such as low level of physical fitness, insufficient physical activity, breakfast skipping, a small number of daily meals, frequent consumption of sweetened beverages, and low educational level of fathers as significant risk factors of IR in adolescents. Recognizing the main lifestyle risk factors and early IR identification is important in terms of the performance of preventive strategies. Weight reduction, regular physical activity, and healthy eating habits can improve insulin sensitivity and decrease the incidence of metabolic syndrome, type 2 diabetes, and cardiovascular disease (CVD).


Sign in / Sign up

Export Citation Format

Share Document