scholarly journals TLR4 at the Crossroads of Nutrients, Gut Microbiota, and Metabolic Inflammation

2015 ◽  
Vol 36 (3) ◽  
pp. 245-271 ◽  
Author(s):  
Licio A. Velloso ◽  
Franco Folli ◽  
Mario J. Saad
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Current Data ◽  
Dietary Fats ◽  
Low Grade ◽  
Metabolic Inflammation

Abstract Obesity is accompanied by the activation of low-grade inflammatory activity in metabolically relevant tissues. Studies have shown that obesity-associated insulin resistance results from the inflammatory targeting and inhibition of key proteins of the insulin-signaling pathway. At least three apparently distinct mechanisms–endoplasmic reticulum stress, toll-like receptor (TLR) 4 activation, and changes in gut microbiota–have been identified as triggers of obesity-associated metabolic inflammation; thus, they are expected to represent potential targets for the treatment of obesity and its comorbidities. Here, we review the data that place TLR4 in the center of the events that connect the consumption of dietary fats with metabolic inflammation and insulin resistance. Changes in the gut microbiota can lead to reduced integrity of the intestinal barrier, leading to increased leakage of lipopolysaccharides and fatty acids, which can act upon TLR4 to activate systemic inflammation. Fatty acids can also trigger endoplasmic reticulum stress, which can be further stimulated by cross talk with active TLR4. Thus, the current data support a connection among the three main triggers of metabolic inflammation, and TLR4 emerges as a link among all of these mechanisms.

scholarly journals Fatty acids from diet and microbiota regulate energy metabolism

F1000Research ◽  
2015 ◽  
Vol 4 ◽  
pp. 738 ◽  
Author(s):  
Joe Alcock ◽  
Henry C. Lin
Keyword(s):  
Insulin Resistance ◽  
Metabolic Syndrome ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Barrier Function ◽  
Unsaturated Fatty Acids ◽  
Intestinal Barrier ◽  
Dietary Fats ◽  
Intestinal Barrier Function ◽  
Metabolic Endotoxemia

A high-fat diet and elevated levels of free fatty acids are known risk factors for metabolic syndrome, insulin resistance, and visceral obesity. Although these disease associations are well established, it is unclear how different dietary fats change the risk of insulin resistance and metabolic syndrome. Here, we review emerging evidence that insulin resistance and fat storage are linked to changes in the gut microbiota. The gut microbiota and intestinal barrier function, in turn, are highly influenced by the composition of fat in the diet. We review findings that certain fats (for example, long-chain saturated fatty acids) are associated with dysbiosis, impairment of intestinal barrier function, and metabolic endotoxemia. In contrast, other fatty acids, including short-chain and certain unsaturated fatty acids, protect against dysbiosis and impairment of barrier function caused by other dietary fats. These fats may promote insulin sensitivity by inhibiting metabolic endotoxemia and dysbiosis-driven inflammation. During dysbiosis, the modulation of metabolism by diet and microbiota may represent an adaptive process that compensates for the increased fuel demands of an activated immune system.

Gut microbiota in health and disease: an overview focused on metabolic inflammation

2016 ◽  
Vol 7 (2) ◽  
pp. 181-194 ◽  
Author(s):  
R. Nagpal ◽  
M. Kumar ◽  
A.K. Yadav ◽  
R. Hemalatha ◽  
H. Yadav ◽  
...  
Keyword(s):  
Type 2 Diabetes ◽  
Metabolic Syndrome ◽  
Gut Microbiota ◽  
Intestinal Barrier ◽  
Adverse Outcomes ◽  
Special Focus ◽  
Low Grade ◽  
Immune Functions ◽  
Metabolic Inflammation

In concern to the continuously rising global prevalence of obesity, diabetes and associated diseases, novel preventive and therapeutic approaches are urgently required. However, to explore and develop such innovative strategies, a meticulous comprehension of the biological basis of these diseases is extremely important. Past decade has witnessed an enormous amount of research investigation and advancement in the field of obesity, diabetes and metabolic syndrome, with the gut microbiota receiving a special focus in the triangle of nutrition, health and diseases. In particular, the role of gut microbiota in health and diseases has been one of the most vigorous and intriguing field of recent research; however, much still remains to be elucidated about its precise role in host metabolism and immune functions and its implication in the onset, progression as well as in the amelioration of metabolic ailments. Recent investigations have suggested a significant contribution of the gut microbiota in the regulation and impairment of energy homeostasis, thereby causing metabolic disorders, such as metabolic endotoxemia, insulin resistance and type 2 diabetes. Numerous inflammatory biomarkers have been found to be associated with obesity, diabetes and risk of other associated adverse outcomes, thereby suggesting that a persistent low-grade inflammatory response is a potential risk factor. In this milieu, this review intends to discuss potential evidences supporting the disturbance of the gut microbiota balance and the intestinal barrier permeability as a potential triggering factor for systemic inflammation in the onset and progression of obesity, type 2 diabetes and metabolic syndrome.

scholarly journals Omega-3 Fatty Acids and Insulin Resistance: Focus on the Regulation of Mitochondria and Endoplasmic Reticulum Stress

Nutrients ◽  
2018 ◽  
Vol 10 (3) ◽  
pp. 350 ◽  
Author(s):  
Marilena Lepretti ◽  
Stefania Martucciello ◽  
Mario Burgos Aceves ◽  
Rosalba Putti ◽  
Lillà Lionetti
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Endoplasmic Reticulum Stress ◽  
Omega 3 Fatty Acids ◽  
Omega 3

scholarly journals Microbiota and Diabetes Mellitus: Role of Lipid Mediators

Nutrients ◽  
2020 ◽  
Vol 12 (10) ◽  
pp. 3039
Author(s):  
Juan Salazar ◽  
Lissé Angarita ◽  
Valery Morillo ◽  
Carla Navarro ◽  
María Sofía Martínez ◽  
...  
Keyword(s):  
Diabetes Mellitus ◽  
Insulin Resistance ◽  
Fatty Acids ◽  
Immune System ◽  
Gut Microbiota ◽  
Eating Habits ◽  
Intestinal Barrier ◽  
Short Chain Fatty Acids ◽  
Lipid Mediators

Diabetes Mellitus (DM) is an inflammatory clinical entity with different mechanisms involved in its physiopathology. Among these, the dysfunction of the gut microbiota stands out. Currently, it is understood that lipid products derived from the gut microbiota are capable of interacting with cells from the immune system and have an immunomodulatory effect. In the presence of dysbiosis, the concentration of lipopolysaccharides (LPS) increases, favoring damage to the intestinal barrier. Furthermore, a pro-inflammatory environment prevails, and a state of insulin resistance and hyperglycemia is present. Conversely, during eubiosis, the production of short-chain fatty acids (SCFA) is fundamental for the maintenance of the integrity of the intestinal barrier as well as for immunogenic tolerance and appetite/satiety perception, leading to a protective effect. Additionally, it has been demonstrated that alterations or dysregulation of the gut microbiota can be reversed by modifying the eating habits of the patients or with the administration of prebiotics, probiotics, and symbiotics. Similarly, different studies have demonstrated that drugs like Metformin are capable of modifying the composition of the gut microbiota, promoting changes in the biosynthesis of LPS, and the metabolism of SCFA.

scholarly journals Feeding diversified protein sources exacerbates hepatic insulin resistance via increased gut microbial branched-chain fatty acids and mTORC1 signaling in obese mice

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Béatrice S.-Y. Choi ◽  
Noëmie Daniel ◽  
Vanessa P. Houde ◽  
Adia Ouellette ◽  
Bruno Marcotte ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Fatty Acids ◽  
Gut Microbiota ◽  
Protein Source ◽  
Hepatic Insulin Resistance ◽  
Branched Chain Fatty Acids ◽  
Mtorc1 Signaling ◽  
Branched Chain ◽  
Mixed Protein ◽  
Chain Fatty Acids

AbstractAnimal models of human diseases are classically fed purified diets that contain casein as the unique protein source. We show that provision of a mixed protein source mirroring that found in the western diet exacerbates diet-induced obesity and insulin resistance by potentiating hepatic mTORC1/S6K1 signaling as compared to casein alone. These effects involve alterations in gut microbiota as shown by fecal microbiota transplantation studies. The detrimental impact of the mixed protein source is also linked with early changes in microbial production of branched-chain fatty acids (BCFA) and elevated plasma and hepatic acylcarnitines, indicative of aberrant mitochondrial fatty acid oxidation. We further show that the BCFA, isobutyric and isovaleric acid, increase glucose production and activate mTORC1/S6K1 in hepatocytes. Our findings demonstrate that alteration of dietary protein source exerts a rapid and robust impact on gut microbiota and BCFA with significant consequences for the development of obesity and insulin resistance.

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