Recruitment of Thermogenic Fat: Trigger of Fat Burning

Brown and beige adipose tissues possess the remarkable capacity to convert energy into heat, which potentially opens novel therapeutic perspectives targeting the epidemic of metabolic syndromes such as obesity and type 2 diabetes. These thermogenic fats implement mitochondrial oxidative phosphorylation and uncouple respiration to catabolize fatty acids and glucose, which leads to an increase in energy expenditure. In particular, beige adipocytes that arise in white adipose tissue display their thermogenic capacity through various noncanonical mechanisms. This review aims to summarize the general overview of thermogenic fat, especially including the UCP1-independent adaptive thermogenesis and the emerging mechanisms of “beiging”, which may provide more evidence of targeting thermogenic fat to counteract obesity and other metabolic disorders in humans.

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A Transcriptomic and Proteomic Atlas of Obesity and Type 2 Diabetes in Cynomolgus Monkeys

10.1101/2021.12.10.472179 ◽

2021 ◽

Author(s):

Xianglong Zhang ◽

Ying Lei ◽

Oliver Homann ◽

Marina Stolina ◽

Songli Wang ◽

...

Keyword(s):

Type 2 Diabetes ◽

Immune Response ◽

Nonhuman Primate ◽

Metabolic Disorders ◽

Healthy Controls ◽

Adipose Tissues ◽

Cynomolgus Monkeys ◽

Single Cell Rna Sequencing

Obesity and type 2 diabetes (T2D) remain major global healthcare challenges and developing therapeutics necessitate using nonhuman primate models. Here, we present transcriptomic and proteomic analyses of all the major organs of cynomolgus monkeys with spontaneous obesity or T2D in comparison to healthy controls. Molecular changes occur predominantly in the adipose tissues of individuals with obesity, while extensive expression perturbations among T2D individuals are observed in many tissues, such as the liver, kidney, brain, and heart. Immune response-related pathways are upregulated in obesity and T2D, whereas metabolism and mitochondrial pathways are downregulated. Incorporating human single-cell RNA sequencing findings corroborates the role of macrophages and monocytes in obesity. Moreover, we highlight some potential therapeutic targets including SLC2A1 and PCSK1 in obesity as well as SLC30A8 and SLC2A2 in T2D. Our findings provide insights into tissue-specific molecular foundations of obesity and T2D and reveal the mechanistic links between these two metabolic disorders.

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Untargeted Metabolomics Analysis Revealed Lipometabolic Disorders in Perirenal Adipose Tissue of Rabbits Subject to a High-Fat Diet

Animals ◽

10.3390/ani11082289 ◽

2021 ◽

Vol 11 (8) ◽

pp. 2289

Author(s):

Siqi Xia ◽

Jiahao Shao ◽

Mauricio A. Elzo ◽

Tao Tang ◽

Yanhong Li ◽

...

Keyword(s):

Insulin Resistance ◽

Type 2 Diabetes ◽

Fatty Acids ◽

High Fat Diet ◽

Metabolic Disorders ◽

Unsaturated Fatty Acids ◽

High Resolution Mass Spectrometry ◽

Untargeted Metabolomics ◽

High Fat

A high-fat diet (HFD) is widely recognized as a significant modifiable risk for insulin resistance, inflammation, Type 2 diabetes, atherosclerosis and other metabolic diseases. However, the biological mechanism responsible for key metabolic disorders in the PAT of rabbits subject to HFD remains unclear. Here, untargeted metabolomics (LC-MS/MS) combined with liquid chromatography (LC) and high-resolution mass spectrometry (MS) were used to evaluate PAT metabolic changes. Histological observations showed that the adipocytes cells and density of PAT were significantly increased in HFD rabbits. Our study revealed 206 differential metabolites (21 up-regulated and 185 down-regulated); 47 differential metabolites (13 up-regulated and 34 down-regulated), comprising mainly phospholipids, fatty acids, steroid hormones and amino acids, were chosen as potential biomarkers to help explain metabolic disorders caused by HFD. These metabolites were mainly associated with the biosynthesis of unsaturated fatty acids, the arachidonic acid metabolic pathway, the ovarian steroidogenesis pathway, and the platelet activation pathway. Our study revealed that a HFD caused significant lipometabolic disorders. These metabolites may inhibit oxygen respiration by increasing the adipocytes cells and density, cause mitochondrial and endoplasmic reticulum dysfunction, produce inflammation, and finally lead to insulin resistance, thus increasing the risk of Type 2 diabetes, atherosclerosis, and other metabolic syndromes.

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Ceramide synthase 6 inhibition as a novel therapeutic approach for obesity and type 2 diabetes

Endocrine Abstracts ◽

10.1530/endoabs.49.gp105 ◽

2017 ◽

Author(s):

Maximilian Bielohuby ◽

Surya Prakash ◽

Bodo Brunner ◽

Anja Pfenninger ◽

Ulrich Werner ◽

...

Keyword(s):

Type 2 Diabetes ◽

Therapeutic Approach ◽

Ceramide Synthase ◽

Novel Therapeutic

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The Relationship between the Gut Microbiome and Metformin as a Key for Treating Type 2 Diabetes Mellitus

International Journal of Molecular Sciences ◽

10.3390/ijms22073566 ◽

2021 ◽

Vol 22 (7) ◽

pp. 3566

Author(s):

Chae Bin Lee ◽

Soon Uk Chae ◽

Seong Jun Jo ◽

Ui Min Jerng ◽

Soo Kyung Bae

Keyword(s):

Diabetes Mellitus ◽

Type 2 Diabetes ◽

Type 2 Diabetes Mellitus ◽

Glucose Metabolism ◽

Gut Microbiome ◽

Metabolic Disorders ◽

Current Knowledge ◽

Potential Target ◽

The Relationship

Metformin is the first-line pharmacotherapy for treating type 2 diabetes mellitus (T2DM); however, its mechanism of modulating glucose metabolism is elusive. Recent advances have identified the gut as a potential target of metformin. As patients with metabolic disorders exhibit dysbiosis, the gut microbiome has garnered interest as a potential target for metabolic disease. Henceforth, studies have focused on unraveling the relationship of metabolic disorders with the human gut microbiome. According to various metagenome studies, gut dysbiosis is evident in T2DM patients. Besides this, alterations in the gut microbiome were also observed in the metformin-treated T2DM patients compared to the non-treated T2DM patients. Thus, several studies on rodents have suggested potential mechanisms interacting with the gut microbiome, including regulation of glucose metabolism, an increase in short-chain fatty acids, strengthening intestinal permeability against lipopolysaccharides, modulating the immune response, and interaction with bile acids. Furthermore, human studies have demonstrated evidence substantiating the hypotheses based on rodent studies. This review discusses the current knowledge of how metformin modulates T2DM with respect to the gut microbiome and discusses the prospect of harnessing this mechanism in treating T2DM.

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The relationship between gut microbiota, short-chain fatty acids and type 2 diabetes mellitus: the possible role of dietary fibre

Acta Diabetologica ◽

10.1007/s00592-021-01727-5 ◽

2021 ◽

Author(s):

Dominic Salamone ◽

Angela Albarosa Rivellese ◽

Claudia Vetrani

Keyword(s):

Type 2 Diabetes ◽

Fatty Acids ◽

Gut Microbiota ◽

Dietary Fibre ◽

Short Chain Fatty Acids ◽

Short Chain ◽

Microbiota Composition ◽

The Relationship ◽

Chain Fatty Acids

AbstractGut microbiota and its metabolites have been shown to influence multiple physiological mechanisms related to human health. Among microbial metabolites, short-chain fatty acids (SCFA) are modulators of different metabolic pathways. On the other hand, several studies suggested that diet might influence gut microbiota composition and activity thus modulating the risk of metabolic disease, i.e. obesity, insulin resistance and type 2 diabetes. Among dietary component, dietary fibre may play a pivotal role by virtue of its prebiotic effect on fibre-fermenting bacteria, that may increase SCFA production. The aim of this review was to summarize and discuss current knowledge on the impact of dietary fibre as modulator of the relationship between glucose metabolism and microbiota composition in humans. More specifically, we analysed evidence from observational studies and randomized nutritional intervention investigating the relationship between gut microbiota, short-chain fatty acids and glucose metabolism. The possible mechanisms behind this association were also discussed.

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