Research Article Details
| Article ID: | A52709 |
| PMID: | 23128765 |
| Source: | Nestle Nutr Inst Workshop Ser |
| Title: | Targeting adipose tissue inflammation to treat the underlying basis of the metabolic complications of obesity. |
| Abstract: | The prevalence of obesity has increased throughout the last three decades due to genetic, metabolic, behavioral, and environmental factors [1]. Obesity in turn increases risk for a number of metabolic diseases including type 2 diabetes, cardiovascular disease, fatty liver disease and some forms of cancer [1]. Despite the well-known link between obesity and increased morbidity, the mechanism of this remains elusive. Thus, the question 'why does increased body fat cause increased metabolic comorbidities' remains unanswered. By understanding the underlying basis of obesity-associated metabolic diseases, different therapies could be designed to target relevant pathways. Although we lack a full understanding of the underlying mechanisms that result in disease, several putative explanations exist for why fat affects metabolic health. One such theory is based on the anatomic location of fat deposition and ectopic fat accumulation [2]. Specifically, current literature suggests that visceral, liver and skeletal fat accumulation affects organ function and contributes to the development of insulin resistance, fatty liver, and the metabolic syndrome [3]. However, even in individuals matched for body fat and fat distribution, significant differences can exist in metabolic outcomes, and the phenomenon of metabolically healthy obese has been well described [4]. More recent data suggest the alternative hypothesis relating excess adipose tissue to disease risk based on the metabolic function and morphological properties of adipose tissue. In this scenario, excess adipose tissue is hypothesized to contribute to a state of chronic inflammation which promotes development of insulin resistance as well as other metabolic complications by stimulating nuclear factor-ĸB and Jun N-terminal kinase pathways in adipocytes and the liver [5]. In this paper, we will review the hypothesis linking excess adipose tissue to increased disease risk through adipose tissue inflammation. |
| DOI: | 10.1159/000341287 |
| Strategy ID | Therapy Strategy | Synonyms | Therapy Targets | Therapy Drugs | |
|---|---|---|---|---|---|
| S08 | Lifestyle measures | Lifestyle intervention; weight loss; diet adaptation; dietary interventions; lifestyle modifications; Exercise | -- | -- | Details |
| 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 |
| 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 |
| 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 | |
|---|---|---|---|---|---|---|---|
| D248 | Obeticholic Acid | Chemical drug | DB05990 | NR1H4 activator; NR1H4 agonist; FXR agonist | Enhance lipid metabolism | Approval rejected | Details |
| D182 | Insulin | Biological drug | DB00030 | INSR agonist; CPE modulator&product of | -- | Under clinical trials | Details |