Research Article Details
| Article ID: | A01138 |
| PMID: | 34858322 |
| Source: | Front Endocrinol (Lausanne) |
| Title: | The Impact of Dysmetabolic Sarcopenia Among Insulin Sensitive Tissues: A Narrative Review. |
| Abstract: | Sarcopenia is a common muscular affection among elderly individuals. More recently, it has been recognized as the skeletal muscle (SM) expression of the metabolic syndrome. The prevalence of sarcopenia is increasing along with visceral obesity, to which it is tightly associated. Nonetheless, it is a still underreported entity by clinicians, despite the worsening in disease burden and reduced patient quality of life. Recognition of sarcopenia is clinically challenging, and variability in study populations and diagnostic methods across the clinical studies makes it hard to reach a strong evidence. Impaired insulin activity in SM is responsible for the altered molecular pathways and clinical manifestations of sarcopenia, which is morphologically expressed by myosteatosis. Lipotoxicity, oxidative stress and adipose tissue-derived inflammation lead to both alterations in glucose disposal and protein synthesis in SM, with raising insulin resistance (IR) and SM atrophy. In particular, hyperleptinemia and leptin resistance interfere directly with SM activity, but also with the release of Growth Hormone from the hypohysis, leading to a lack in its anabolic effect on SM. Moreover, sarcopenia is independently associated to liver fibrosis in Non-Alcoholic Fatty Liver Disease (NAFLD), which in turn worsens SM functionality through the secretion of proinflammatory heptokines. The cross-talk between the liver and SM in the IR setting is of crucial relevance, given the high prevalence of NAFLD and the reciprocal impact of insulin-sensitive tissues on the overall disease burden. Along with the efforts of non-invasive diagnostic approaches, irisin and myostatin are two myokines currently evaluated as potential biomarkers for diagnosis and prognostication. Decreased irisin levels seem to be potentially associated to sarcopenia, whereas increased myostatin has shown to negatively impact on sarcopenia in pre-clinical studies. Gene variants in irisin have been explored with regard to the impact on the liver disease phenotype, with conflicting results. The gut-muscle axis has gain relevance with the evidence that insulin resistance-derived gut dysbiosis is responsible for increased endotoxemia and reduction in short-chain free fatty acids, directly affecting and predisposing to sarcopenia. Based on the current evidence, more efforts are needed to increase awareness and improve the management of sarcopenic patients. |
| DOI: | 10.3389/fendo.2021.716533 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S01 | Improve insulin resistance | insulin sensitizer; insulin resistance; glucose tolerance | Biguanide: increases 5-AMP activated protein kinase signaling; SGLT-2 inhibitor; Thiazalidinedione: selective PPAR-γ agonists; GLP-1 agonist | Metformin; Empagliflozin; Canagliflozin; Rosiglitazone; Pioglitazone; Liraglutide | Details |
| S03 | Anti-fibrosis | fibrosis | Angiotensin Receptor Blocker (ARB); CCR2/CCR5 antagonist; Thyroid receptor β agonist; PEGylated human FGF21 analogue; Monoclonal antibody to lysyl oxidase-like 2 (LOXL2); Galectin-3 inhibitor; FGF19 variant | Losartan; Cenicriviroc; VK-2809; MGL-3196; Pegbelfermin; Simtuzumab; GR-MD-02; NGM282 | Details |
| S04 | Anti-oxidative stress | oxidative stress | α-tocopherol: antioxidant | Vitamin E | Details |
| S05 | Anti-inflammatory | inflammatory | Bile acid; TNF-a inhibitor; Dual PPAR-α and -δ agonists; Toll-Like Receptor; (TLR)-4 antagonist; Caspase inhibitor; ASK-1 inhibitor | Ursodeoxycholic Acid; Pentoxifylline; Elafibranor; JKB-121; Emricasan; Selonsertib; | Details |
| Target ID | Target Name | GENE | Action | Class | UniProtKB ID | Entry Name |
|---|
| Diseases ID | DO ID | Disease Name | Definition | Class | |
|---|---|---|---|---|---|
| I05 | 9352 | Type 2 diabetes mellitus | A diabetes that is characterized by chronic hyperglycaemia with disturbances of carbohydrate, fat and protein metabolism resulting from defects in insulin secretion, insulin action, or both. A diabetes mellitus that is characterized by high blood sugar, insulin resistance, and relative lack of insulin. http://en.wikipedia.org/wiki/Diabetes, http://en.wikipedia.org/wiki/Diabetes_mellitus_type_2 | disease of metabolism/inherited metabolic disorder/ carbohydrate metabolic disorder/glucose metabolism disease/diabetes/ diabetes mellitus | Details |
| I14 | 9970 | Obesity | An overnutrition that is characterized by excess body fat, traditionally defined as an elevated ratio of weight to height (specifically 30 kilograms per meter squared), has_material_basis_in a multifactorial etiology related to excess nutrition intake, decreased caloric utilization, and genetic susceptibility, and possibly medications and certain disorders of metabolism, endocrine function, and mental illness. https://en.wikipedia.org/wiki/Obesity | disease of metabolism/acquired metabolic disease/ nutrition disease/overnutrition | Details |
| Drug ID | Drug Name | Type | DrugBank ID | Targets | Category | Latest Progress | |
|---|---|---|---|---|---|---|---|
| D160 | Growth Hormone | Biological drug | DB00052 | GHR ligand; PRLR ligand | -- | Under clinical trials | Details |
| D579 | Emfilermin | Miscellany | -- | adipocytes | Enhance lipid metabolism | Under investigation | Details |
| D010 | Amoxicillin | Chemical drug | DB01060 | -- | -- | Under clinical trials | Details |
| D080 | Citrulline | Chemical drug | DB00155 | -- | -- | Under clinical trials | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |
| D343 | Somatropin | Biological drug | DB00052 | GHR ligand; PRLR ligand | Hormone replacement drug | Under clinical trials | Details |
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |