Mechanisms of muscle insulin resistance and the cross‐talk with liver and adipose tissue

Rosa, Simone C. da Silva; Nayak, Nichole; Caymo, Andrei Miguel; Gordon, Joseph W.

doi:10.14814/phy2.14607

Cited by 120 publications

(81 citation statements)

References 215 publications

(286 reference statements)

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The result of the impaired suppression of lipolysis is an increased release of FFAs and glycerol into the bloodstream and ectopic fat accumulation [ 38 ]. Among ectopic lipids, toxic species such as DAG and ceramides can disrupt insulin signaling by inhibiting insulin receptor and Akt activation [ 39 ]. Adipose tissue IR has also been linked to mitochondrial dysfunction and mitophagy; decreased mitochondrial biogenesis and reduced mitochondrial oxidative protein content lead to a reduced oxidative capacity [ 40 , 41 ].…”

Section: Metabolic Effects Of Insulinmentioning

confidence: 99%

Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease

et al. 2021

View full text Add to dashboard Cite

Insulin resistance (IR) is defined as a lower-than-expected response to insulin action from target tissues, leading to the development of type 2 diabetes through the impairment of both glucose and lipid metabolism. IR is a common condition in subjects with nonalcoholic fatty liver disease (NAFLD) and is considered one of the main factors involved in the pathogenesis of nonalcoholic steatohepatitis (NASH) and in the progression of liver disease. The liver, the adipose tissue and the skeletal muscle are major contributors for the development and worsening of IR. In this review, we discuss the sites and mechanisms of insulin action and the IR-related impairment along the spectrum of NAFLD, from simple steatosis to progressive NASH and cirrhosis.

show abstract

Section: Metabolic Effects Of Insulinmentioning

confidence: 99%

Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease

et al. 2021

View full text Add to dashboard Cite

show abstract

“…The proposed mechanisms involved in insulin resistance include both whole body aspects, such as inflammation and metabolic inflexibility; as well as cellular phenomena, such as lipotoxicity, ER stress, and mitochondrial dysfunction. Lipotoxicity, as a result of increased lipolysis in AT and release of FFAs, is a type of cellular stress induced by the accumulation of lipid intermediates such as diacylglycerols (DAGs), ceramides, and triglycerides that facilitate the development of insulin resistance and ectopic fat deposition in muscle, liver, and adipose tissue together with a proinflammatory response (177). Lipotoxicity participates to the enhanced cardiometabolic risk observed in PLWH (178,179).…”

Section: Insulin Resistance and Lipotoxicitymentioning

confidence: 99%

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

et al. 2021

View full text Add to dashboard Cite

White adipose tissue (AT) contributes significantly to inflammation – especially in the context of obesity. Several of AT’s intrinsic features favor its key role in local and systemic inflammation: (i) large distribution throughout the body, (ii) major endocrine activity, and (iii) presence of metabolic and immune cells in close proximity. In obesity, the concomitant pro-inflammatory signals produced by immune cells, adipocytes and adipose stem cells help to drive local inflammation in a vicious circle. Although the secretion of adipokines by AT is a prime contributor to systemic inflammation, the lipotoxicity associated with AT dysfunction might also be involved and could affect distant organs. In HIV-infected patients, the AT is targeted by both HIV infection and antiretroviral therapy (ART). During the primary phase of infection, the virus targets AT directly (by infecting AT CD4 T cells) and indirectly (via viral protein release, inflammatory signals, and gut disruption). The initiation of ART drastically changes the picture: ART reduces viral load, restores (at least partially) the CD4 T cell count, and dampens inflammatory processes on the whole-body level but also within the AT. However, ART induces AT dysfunction and metabolic side effects, which are highly dependent on the individual molecules and the combination used. First generation thymidine reverse transcriptase inhibitors predominantly target mitochondrial DNA and induce oxidative stress and adipocyte death. Protease inhibitors predominantly affect metabolic pathways (affecting adipogenesis and adipocyte homeostasis) resulting in insulin resistance. Recently marketed integrase strand transfer inhibitors induce both adipocyte adipogenesis, hypertrophy and fibrosis. It is challenging to distinguish between the respective effects of viral persistence, persistent immune defects and ART toxicity on the inflammatory profile present in ART-controlled HIV-infected patients. The host metabolic status, the size of the pre-established viral reservoir, the quality of the immune restoration, and the natural ageing with associated comorbidities may mitigate and/or reinforce the contribution of antiretrovirals (ARVs) toxicity to the development of low-grade inflammation in HIV-infected patients. Protecting AT functions appears highly relevant in ART-controlled HIV-infected patients. It requires lifestyle habits improvement in the absence of effective anti-inflammatory treatment. Besides, reducing ART toxicities remains a crucial therapeutic goal.

show abstract

“…Studies indicate that the disproportionate release of pro-inflammatory adipokines and the reduction in lipolysis are simultaneous with insulin resistance, which plays a substantial role in the development of DM2. Insulin suppression leads to an increase in plasma fatty acid and consequent absorption by liver and muscle tissue, creating intracellular lipotoxic environments that prevent the translocation of GLUT4 in skeletal muscles and adipose tissue [ 104 , 105 ]. Substances that act as adipokines, myokines, and hepatokines, such as FGF21, are essential for controlling glucose and lipid metabolism.…”

Section: Discussionmentioning

confidence: 99%

Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

Santos

Zanuso

Miola

et al. 2021

IJMS

113

111

View full text Add to dashboard Cite

Adipose, skeletal, and hepatic muscle tissues are the main endocrine organs that produce adipokines, myokines, and hepatokines. These biomarkers can be harmful or beneficial to an organism and still perform crosstalk, acting through the endocrine, paracrine, and autocrine pathways. This study aims to review the crosstalk between adipokines, myokines, and hepatokines. Far beyond understanding the actions of each biomarker alone, it is important to underline that these cytokines act together in the body, resulting in a complex network of actions in different tissues, which may have beneficial or non-beneficial effects on the genesis of various physiological disorders and their respective outcomes, such as type 2 diabetes mellitus (DM2), obesity, metabolic syndrome, and cardiovascular diseases (CVD). Overweight individuals secrete more pro-inflammatory adipokines than those of a healthy weight, leading to an impaired immune response and greater susceptibility to inflammatory and infectious diseases. Myostatin is elevated in pro-inflammatory environments, sharing space with pro-inflammatory organokines, such as tumor necrosis factor-alpha (TNF-α), interleukin-1 (IL-1), resistin, and chemerin. Fibroblast growth factor FGF21 acts as a beta-oxidation regulator and decreases lipogenesis in the liver. The crosstalk mentioned above can interfere with homeostatic disorders and can play a role as a potential therapeutic target that can assist in the methods of diagnosing metabolic syndrome and CVD.

show abstract

Mechanisms of muscle insulin resistance and the cross‐talk with liver and adipose tissue

Abstract: This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.

Cited by 120 publications

References 215 publications

Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease

Insulin Resistance across the Spectrum of Nonalcoholic Fatty Liver Disease

Contribution of Adipose Tissue to the Chronic Immune Activation and Inflammation Associated With HIV Infection and Its Treatment

Adipokines, Myokines, and Hepatokines: Crosstalk and Metabolic Repercussions

Contact Info

Product

Resources

About