Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Turner, Nigel; Cooney, Gregory J.; Kraegen, Edward W.; Bruce, Clinton R.

doi:10.1530/joe-13-0397

Cited by 161 publications

(131 citation statements)

References 192 publications

Supporting

Mentioning

124

Contrasting

Unclassified

Order By: Relevance

“…However, triacylglycerol, the main storage form of lipid, is not considered to be mechanistically linked with the development of IR (reviewed in Turner et al 2014). Instead, the more bioactive derivatives ceramide and diacylglycerol have direct inhibitory effects on insulin signalling and metabolism (Chibalin et al 2008, Ussher et al 2010.…”

Section: Possible Mechanisms: Accumulation Of Intramyocellular Lipid mentioning

confidence: 99%

Insulin resistance and sarcopenia: mechanistic links between common co-morbidities

Cleasby

Jamieson

Atherton

2016

Journal of Endocrinology

388

296

View full text Add to dashboard Cite

Insulin resistance (IR) in skeletal muscle is a key defect mediating the link between obesity and type 2 diabetes, a disease that typically affects people in later life. Sarcopenia (age-related loss of muscle mass and quality) is a risk factor for a number of frailty-related conditions that occur in the elderly. In addition, a syndrome of 'sarcopenic obesity' (SO) is now increasingly recognised, which is common in older people and is applied to individuals that simultaneously show obesity, IR and sarcopenia. Such individuals are at an increased risk of adverse health events compared with those who are obese or sarcopenic alone. However, there are no licenced treatments for sarcopenia or SO, the syndrome is poorly defined clinically and the mechanisms that might explain a common aetiology are not yet well characterised. In this review, we detail the nature and extent of the clinical syndrome, highlight some of the key physiological processes that are dysregulated and discuss some candidate molecular pathways that could be implicated in both metabolic and anabolic defects in skeletal muscle, with an eye towards future therapeutic options. In particular, the potential roles of Akt/mammalian target of rapamycin signalling, AMP-activated protein kinase, myostatin, urocortins and vitamin D are discussed. R67-R81 229:2 Muscle insulin resistance and sarcopenia Associations between obesity, diabetes and skeletal muscle ageingThe International Diabetes Federation has estimated that there were 382 million people living with diabetes in 2013, with this number predicted to rise to 592 million by 2035, of which the significant majority would be of >40 years old (IDF 2013). Of these, 90% suffer from type 2 diabetes (T2D), which is characterised by both β-cell failure and resistance to the actions of insulin at the tissue level (insulin resistance, IR). As skeletal muscle is responsible for the majority of the body's postprandial glucose disposal, IR in this tissue results in substantial whole-body metabolic disturbances. However, it is likely that the metabolic disturbances associated with T2D are further exacerbated by the marked loss of skeletal muscle mass that can also be associated with these conditions (Park et al. 2009, Kim et al. 2010. Specifically, loss of muscle mass induces a 2-3% decline in basal metabolic rate per decade after the age of 20 years and 4% per decade after the age of 50 years, resulting from concomitant loss of mitochondrial volume density and oxidative capacity (Conley et al. 2000). Journal of EndocrinologyThis loss of muscle mass in the elderly is also the principal factor responsible for 'frailty', a syndrome that has been clinically defined as the possession of three of: unintentional weight loss (10 pounds (~4.5 kg) in the past year), self-reported exhaustion, weakness (poor grip strength), slow walking speed and low physical activity (Fried et al. 2001). Loss of muscle mass (atrophy) is an inevitable, although somewhat modifiable, process that occurs with ageing (Sayer et al. 2008), w...

show abstract

Section: Possible Mechanisms: Accumulation Of Intramyocellular Lipid mentioning

confidence: 99%

Insulin resistance and sarcopenia: mechanistic links between common co-morbidities

Cleasby

Jamieson

Atherton

2016

Journal of Endocrinology

388

296

View full text Add to dashboard Cite

show abstract

“…1, is growing. The increased level of both lipid fractions has been reported in the muscular tissue of obese humans and rodents [24,25]. Furthermore, interventions aiming to reduce the synthesis of CER [23,26] and/or DAG [8] have proven successful in restoring insulin sensitivity in skeletal muscles.…”

Section: Bioactive Lipid Intermediates and Insulin Signaling Pathwaymentioning

confidence: 99%

“…Furthermore, interventions aiming to reduce the synthesis of CER [23,26] and/or DAG [8] have proven successful in restoring insulin sensitivity in skeletal muscles. Moreover, some beneficial effects of exercise training have been attributed to reductions in muscular DAG and CER content [25]. …”

Section: Bioactive Lipid Intermediates and Insulin Signaling Pathwaymentioning

confidence: 99%

“…Secondly, it interferes with the phosphorylation of PKB (via PKCζ) thus leaving PKB in an inactive state and preventing further insulin signal transduction [7,29]. In addition, ceramide may also activate c-Jun N-terminal kinase (JNK), a well-known protein kinase involved in inflammatory responses [7,25]. However, Lee and co-workers [30] have demonstrated in an immuno-compromised rodent model (Jun NH(2)-terminal kinase-deficient mice), that a short term (3 days) high fat diet (HFD) feeding was able to induce IR, independent of inflammation.…”

Section: Bioactive Lipid Intermediates and Insulin Signaling Pathwaymentioning

confidence: 99%

See 1 more Smart Citation

The Role of PGC-1α in the Development of Insulin Resistance in Skeletal Muscle - Revisited

Łukaszuk

Kurek

Mikłosz

et al. 2015

Cell Physiol Biochem

View full text Add to dashboard Cite

Currently, obesity is a predominant medical condition and an important risk factor for the development of several diseases, including type 2 diabetes mellitus. Importantly, most research has indicated lipid-induced insulin resistance in skeletal muscles is a key link between the aforementioned pathological conditions. PGC-1α is a prominent regulator of myocellular energy metabolism orchestrating gene transcription programming in response to numerous environmental stimuli. Moreover, it is widely acknowledged that mitochondrial metabolism (primary metabolic target of PGC-1α) disturbances are widely acknowledged contributors to type 2 diabetes development. Therefore, it seems surprising that the exact physiological contribution of PGC-1α in the development of insulin resistance in skeletal muscle remains poorly understood. This review aims to reconcile these allegedly different findings by looking for a common denominator in the role(s) of PGC-1α in respect to lipid-induced insulin resistance in skeletal muscle. Our scrutiny of the literature indicates that interventions at the level of PGC-1α may exert beneficial effects on myocytes in respect to lipid-induced insulin resistance. The latter takes place as a result of a positive net energy balance (fatty acids oxidation surpassing their accumulation rate). Moreover, the aforementioned effects may not necessarily be limited to physically active states. They seem to occur, however, only within a physiologically observed range in muscle cells (approximately 1-fold changes in PGC-1α protein expression).

show abstract

“…Together with caloric restriction, exercise is a mainstay of a healthy life style and contributes to the control of metabolic efficiency. In addition to converting energy into movement, exercise increases the rates of lipolysis and fat oxidation, promotes heat dissipation (49,53), and causes long-term changes in the expression of numerous genes, including IL-15R␣/IL-15 (55).…”

mentioning

confidence: 99%

IL-15Rα is a determinant of muscle fuel utilization, and its loss protects against obesity

Loro

Seifert

Moffat

et al. 2015

American Journal of Physiology-Regulatory, Integrative and Comp

View full text Add to dashboard Cite

is the widely expressed primary binding partner for IL-15. Because of the wide distribution in nonlymphoid tissues like skeletal muscle, adipose, or liver, IL-15/IL-15R␣ take part in physiological and metabolic processes not directly related to immunity. In fast muscle, lack of IL-15R␣ promotes an oxidative switch, with increased mitochondrial biogenesis and fatigue resistance. These effects are predicted to reproduce some of the benefits of exercise and, therefore, improve energy homeostasis. However, the direct effects of IL-15R␣ on metabolism and obesity are currently unknown. We report that mice lacking IL-15R␣ (IL-15R␣ Ϫ/Ϫ ) are resistant to diet-induced obesity (DIO). High-fat diet-fed IL-15R␣ Ϫ/Ϫ mice have less body and liver fat accumulation than controls. The leaner phenotype is associated with increased energy expenditure and enhanced fatty acid oxidation by muscle mitochondria. Despite being protected against DIO, IL-15R␣ Ϫ/Ϫ are hyperglycemic and insulin-resistant. These findings identify novel roles for IL-15R␣ in metabolism and obesity.interleukin-15 receptor alpha; diet-induced obesity; muscle; fatty acid oxidation; fatigue recovery; glucose homeostasis ACCUMULATION OF EXCESSIVE body fat is a physiological consequence of unnecessary caloric intake. With greater worldwide food production, often the caloric intake largely exceeds the physiological energy requirements, and as a result, the obesity pandemic is growing at alarming rates in both developed and developing countries (21,47). Apart from the role of environmental factors, particularly an energy-dense diet and sedentary lifestyle, obesity also has important genetic determinants that have been conserved across species. Identifying the molecular mechanisms regulating metabolic efficiency (the capacity to convert energy intake into storable energy forms) is of great interest because of the low success in using caloric restriction as a means to manage obesity. Indeed, a number of pathways have been recently identified that reduce the extent of dietinduced obesity (DIO) by decreasing metabolic efficiency rather than energy input (8,10,11,43,56,59,60). Targeting these pathways with pharmacological approaches may also have the advantage of reproducing some of the benefits normally associated with physical exercise. Together with caloric restriction, exercise is a mainstay of a healthy life style and contributes to the control of metabolic efficiency. In addition to converting energy into movement, exercise increases the rates of lipolysis and fat oxidation, promotes heat dissipation (49, 53), and causes long-term changes in the expression of numerous genes, including IL-15R␣/IL-15 (55).IL-15 and its primary binding partner IL-15R␣ have emerged as important regulators of cell functions in both lymphoid and nonlymphoid tissues. Their transcripts are detectable in a variety of tissues, including skeletal muscle, liver, or adipose (http://biogps.org/#gotoϭwelcome). Some of the proposed noncanonical roles of IL-15/IL-15R␣ signaling are mediating anabolic...

show abstract

Fatty acid metabolism, energy expenditure and insulin resistance in muscle

Cited by 161 publications

References 192 publications

Insulin resistance and sarcopenia: mechanistic links between common co-morbidities

Insulin resistance and sarcopenia: mechanistic links between common co-morbidities

The Role of PGC-1α in the Development of Insulin Resistance in Skeletal Muscle - Revisited

IL-15Rα is a determinant of muscle fuel utilization, and its loss protects against obesity

Contact Info

Product

Resources

About