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PLoS ONE ◽  
2021 ◽  
Vol 16 (12) ◽  
pp. e0260765
Author(s):  
Christian Clement Yde ◽  
Henrik Max Jensen ◽  
Niels Christensen ◽  
Florence Servant ◽  
Benjamin Lelouvier ◽  
...  

The past two decades of research have raised gut microbiota composition as a contributing factor to the development of obesity, and higher abundance of certain bacterial species has been linked to the lean phenotype, such as Akkermansia muciniphila. The ability of pre- and probiotics to affect metabolic health could be via microbial community alterations and subsequently changes in metabolite profiles, modulating for example host energy balance via complex signaling pathways. The aim of this mice study was to determine how administration of a prebiotic fiber, polydextrose (PDX) and a probiotic Bifidobacterium animalis ssp. lactis 420 (B420), during high fat diet (HFD; 60 kcal% fat) affects microbiota composition in the gastrointestinal tract and adipose tissue, and metabolite levels in gut and liver. In this study C57Bl/6J mice (N = 200) were split in five treatments and daily gavaged: 1) Normal control (NC); 2) HFD; 3) HFD + PDX; 4) HFD + B420 or 5) HFD + PDX + B420 (HFD+S). At six weeks of treatment intraperitoneal glucose-tolerance test (IPGTT) was performed, and feces were collected at weeks 0, 3, 6 and 9. At end of the intervention, ileum and colon mucosa, adipose tissue and liver samples were collected. The microbiota composition in fecal, ileum, colon and adipose tissue was analyzed using 16S rDNA sequencing, fecal and liver metabolomics were performed by nuclear magnetic resonance (NMR) spectroscopy. It was found that HFD+PDX intervention reduced body weight gain and hepatic fat compared to HFD. Sequencing the mice adipose tissue (MAT) identified Akkermansia and its prevalence was increased in HFD+S group. Furthermore, by the inclusion of PDX, fecal, lleum and colon levels of Akkermansia were increased and liver health was improved as the detoxification capacity and levels of methyl-donors were increased. These new results demonstrate how PDX and B420 can affect the interactions between gut, liver and adipose tissue.


Author(s):  
Víctor J. Costela Ruiz ◽  
Lucía Melguizo Rodríguez ◽  
Rebeca Illescas Montes ◽  
Enrique García Recio ◽  
Salvador Arias Santiago ◽  
...  

2021 ◽  
Author(s):  
Ana Elena Espinosa De Ycaza ◽  
Esben Søndergaard ◽  
Maria Morgan-Bathke ◽  
Kelli Lytle ◽  
Danae A. Delivanis ◽  
...  

The role of adipose tissue (AT) inflammation on AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC<sub>50</sub>). We studied 86 volunteers with normal weight or obesity at baseline, and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong, positive relationship between IC<sub>50 </sub>and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC<sub>50 </sub>and abdominal AT inflammatory markers: CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6 and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC<sub>50</sub>, however, there was no reduction in adipose ATM content, senescent cells or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.


2021 ◽  
pp. 1-8
Author(s):  
M. Shaker ◽  
G.R. Khamisipour ◽  
H. Sadeghipour ◽  
A. Zar ◽  
B. Naeimi ◽  
...  

Diabetes is one of the most important endocrine diseases in the world and obesity is one of the risk factors for this disease. The aim of this study was to evaluate the effect of a resistance exercise and garlic extract on insulin sensitivity/resistance and signal pathway of white adipose tissue to brown factors in diabetic rats. A total of 48 male Wistar rats weighing 180 to 250 g were divided into six groups (n=8): healthy control (C), diabetic control (D), diabetic with garlic extract at a dose of 50 mg/kg body weight (bw) (D+50), diabetic with garlic extract dose of 200 mg/kg bw (D+200), diabetic resistance training (D+Ex), and diabetic resistance training with garlic extract dose of 200 mg/kg bw (D+Ex+200). Plasma irisin levels in the D+200 and D+Ex groups, as well as the D+Ex+200 group showed a significant increase compared to the D group (P<0.001), while in the D+50 group no significant change was observed. Compared with group D, the expression of peroxisome proliferator-activated receptor-gamma coactivator (PGC)-1α gene was significantly increased in groups D+200 and D+Ex, as well as group D+Ex+200 (P<0.001). It can be said that resistance exercise with garlic extract is effective in controlling diabetes and reducing its complications. It also increases the expression of PGC-1α and uncoupling protein 1 genes in white adipose tissue and therefore has a positive effect on beta cell function by irisin.


2021 ◽  
Author(s):  
Ana Elena Espinosa De Ycaza ◽  
Esben Søndergaard ◽  
Maria Morgan-Bathke ◽  
Kelli Lytle ◽  
Danae A. Delivanis ◽  
...  

The role of adipose tissue (AT) inflammation on AT function in humans is unclear. We tested whether AT macrophage (ATM) content, cytokine gene expression and senescent cell burden (markers of AT inflammation) predict AT insulin resistance measured as the insulin concentration that suppresses lipolysis by 50% (IC<sub>50</sub>). We studied 86 volunteers with normal weight or obesity at baseline, and a subgroup of 25 volunteers with obesity before and after weight loss. There was a strong, positive relationship between IC<sub>50 </sub>and abdominal subcutaneous and femoral fat cell size (FCS). The positive, univariate relationships between IC<sub>50 </sub>and abdominal AT inflammatory markers: CD68, CD14, CD206 ATM/100 adipocytes, senescent cells, IL-6 and TNF-α mRNA were not significant after adjustment for FCS. A 10% weight loss significantly reduced IC<sub>50</sub>, however, there was no reduction in adipose ATM content, senescent cells or cytokine gene expression. Our study suggests that commonly used markers of AT inflammation are not causally linked to AT insulin resistance, whereas FCS is a strong predictor of AT insulin resistance with respect to lipolysis.


Diabetes ◽  
2021 ◽  
pp. db210609
Author(s):  
Ana Elena Espinosa De Ycaza ◽  
Esben Søndergaard ◽  
Maria Morgan-Bathke ◽  
Kelli Lytle ◽  
Danae A. Delivanis ◽  
...  

2021 ◽  
Vol 12 ◽  
Author(s):  
Juan P. Palavicini ◽  
Alberto Chavez-Velazquez ◽  
Marcel Fourcaudot ◽  
Devjit Tripathy ◽  
Meixia Pan ◽  
...  

The insulin-sensitizer pioglitazone exerts its cardiometabolic benefits in type 2 diabetes (T2D) through a redistribution of body fat, from ectopic and visceral areas to subcutaneous adipose depots. Whereas excessive weight gain and lipid storage in obesity promotes insulin resistance and chronic inflammation, the expansion of subcutaneous adipose by pioglitazone is associated with a reversal of these immunometabolic deficits. The precise events driving this beneficial remodeling of adipose tissue with pioglitazone remain unclear, and whether insulin-sensitizers alter the lipidomic composition of human adipose has not previously been investigated. Using shotgun lipidomics, we explored the molecular lipid responses in subcutaneous adipose tissue following 6months of pioglitazone treatment (45mg/day) in obese humans with T2D. Despite an expected increase in body weight following pioglitazone treatment, no robust effects were observed on the composition of storage lipids (i.e., triglycerides) or the content of lipotoxic lipid species (e.g., ceramides and diacylglycerides) in adipose tissue. Instead, pioglitazone caused a selective remodeling of the glycerophospholipid pool, characterized by a decrease in lipids enriched for arachidonic acid, such as plasmanylethanolamines and phosphatidylinositols. This contributed to a greater overall saturation and shortened chain length of fatty acyl groups within cell membrane lipids, changes that are consistent with the purported induction of adipogenesis by pioglitazone. The mechanism through which pioglitazone lowered adipose tissue arachidonic acid, a major modulator of inflammatory pathways, did not involve alterations in phospholipase gene expression but was associated with a reduction in its precursor linoleic acid, an effect that was also observed in skeletal muscle samples from the same subjects. These findings offer important insights into the biological mechanisms through which pioglitazone protects the immunometabolic health of adipocytes in the face of increased lipid storage.


2021 ◽  
Author(s):  
Mingsheng Ye ◽  
Liping Luo ◽  
Qi Guo ◽  
Guanghua Lei ◽  
Chao Zeng ◽  
...  

Brown adipose tissue (BAT) is emerging as a target to beat obesity through the dissipation of chemical energy to heat. However, the molecular mechanisms of brown adipocyte thermogenesis remain to be further elucidated. Here, we show that KCTD10, a member of the polymerase delta-interacting protein 1 (PDIP1) family, was reduced in BAT by cold stress and a β3 adrenoceptor agonist. Moreover, KCTD10 level increased in the BAT of obese mice, and KCTD10 overexpression attenuates uncoupling protein 1 (UCP1) expression in primary brown adipocytes. BAT-specific KCTD10 knockdown mice had increased thermogenesis and cold tolerance protecting from high fat diet (HFD)-induced obesity. Conversely, overexpression of KCTD10 in BAT caused reduced thermogenesis, cold intolerance, and obesity. Mechanistically, inhibiting Notch signaling restored the KCTD10 overexpression suppressed thermogenesis. Our study presents that KCTD10 serves as an upstream regulator of notch signaling pathway to regulate BAT thermogenesis and whole-body metabolic function.


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