scholarly journals Interorgan Metabolic Crosstalk in Human Insulin Resistance

2018 ◽  
Vol 98 (3) ◽  
pp. 1371-1415 ◽  
Author(s):  
Sofiya Gancheva ◽  
Tomas Jelenik ◽  
Elisa Álvarez-Hernández ◽  
Michael Roden
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Energy Homeostasis ◽  
Metabolic Diseases ◽  
Short Chain Fatty Acids ◽  
Fatty Acid Esters

Excessive energy intake and reduced energy expenditure drive the development of insulin resistance and metabolic diseases such as obesity and type 2 diabetes mellitus. Metabolic signals derived from dietary intake or secreted from adipose tissue, gut, and liver contribute to energy homeostasis. Recent metabolomic studies identified novel metabolites and enlarged our knowledge on classic metabolites. This review summarizes the evidence of their roles as mediators of interorgan crosstalk and regulators of insulin sensitivity and energy metabolism. Circulating lipids such as free fatty acids, acetate, and palmitoleate from adipose tissue and short-chain fatty acids from the gut effectively act on liver and skeletal muscle. Intracellular lipids such as diacylglycerols and sphingolipids can serve as lipotoxins by directly inhibiting insulin action in muscle and liver. In contrast, fatty acid esters of hydroxy fatty acids have been recently shown to exert a series of beneficial effects. Also, ketoacids are gaining interest as potent modulators of insulin action and mitochondrial function. Finally, branched-chain amino acids not only predict metabolic diseases, but also inhibit insulin signaling. Here, we focus on the metabolic crosstalk in humans, which regulates insulin sensitivity and energy homeostasis in the main insulin-sensitive tissues, skeletal muscle, liver, and adipose tissue.

Lipoprotein lipase: from gene to obesity

2009 ◽  
Vol 297 (2) ◽  
pp. E271-E288 ◽  
Author(s):  
Hong Wang ◽  
Robert H. Eckel
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Adipose Tissue ◽  
Lipoprotein Lipase ◽  
Insulin Action ◽  
Specific Activity ◽  
Neutral Lipids ◽  
Specific Substrate ◽  
Tissue Specific

Lipoprotein lipase (LPL) is a multifunctional enzyme produced by many tissues, including adipose tissue, cardiac and skeletal muscle, islets, and macrophages. LPL is the rate-limiting enzyme for the hydrolysis of the triglyceride (TG) core of circulating TG-rich lipoproteins, chylomicrons, and very low-density lipoproteins (VLDL). LPL-catalyzed reaction products, fatty acids, and monoacylglycerol are in part taken up by the tissues locally and processed differentially; e.g., they are stored as neutral lipids in adipose tissue, oxidized, or stored in skeletal and cardiac muscle or as cholesteryl ester and TG in macrophages. LPL is regulated at transcriptional, posttranscriptional, and posttranslational levels in a tissue-specific manner. Nutrient states and hormonal levels all have divergent effects on the regulation of LPL, and a variety of proteins that interact with LPL to regulate its tissue-specific activity have also been identified. To examine this divergent regulation further, transgenic and knockout murine models of tissue-specific LPL expression have been developed. Mice with overexpression of LPL in skeletal muscle accumulate TG in muscle, develop insulin resistance, are protected from excessive weight gain, and increase their metabolic rate in the cold. Mice with LPL deletion in skeletal muscle have reduced TG accumulation and increased insulin action on glucose transport in muscle. Ultimately, this leads to increased lipid partitioning to other tissues, insulin resistance, and obesity. Mice with LPL deletion in the heart develop hypertriglyceridemia and cardiac dysfunction. The fact that the heart depends increasingly on glucose implies that free fatty acids are not a sufficient fuel for optimal cardiac function. Overall, LPL is a fascinating enzyme that contributes in a pronounced way to normal lipoprotein metabolism, tissue-specific substrate delivery and utilization, and the many aspects of obesity and other metabolic disorders that relate to energy balance, insulin action, and body weight regulation.

Interactions between insulin and exercise

2021 ◽  
Vol 478 (21) ◽  
pp. 3827-3846
Author(s):  
Erik A. Richter ◽  
Lykke Sylow ◽  
Mark Hargreaves
Keyword(s):  
Physical Activity ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Regular Exercise ◽  
Fuel Storage ◽  
Storage Effects ◽  
Glucose Storage ◽  
Glycogen Stores

The interaction between insulin and exercise is an example of balancing and modifying the effects of two opposing metabolic regulatory forces under varying conditions. While insulin is secreted after food intake and is the primary hormone increasing glucose storage as glycogen and fatty acid storage as triglycerides, exercise is a condition where fuel stores need to be mobilized and oxidized. Thus, during physical activity the fuel storage effects of insulin need to be suppressed. This is done primarily by inhibiting insulin secretion during exercise as well as activating local and systemic fuel mobilizing processes. In contrast, following exercise there is a need for refilling the fuel depots mobilized during exercise, particularly the glycogen stores in muscle. This process is facilitated by an increase in insulin sensitivity of the muscles previously engaged in physical activity which directs glucose to glycogen resynthesis. In physically trained individuals, insulin sensitivity is also higher than in untrained individuals due to adaptations in the vasculature, skeletal muscle and adipose tissue. In this paper, we review the interactions between insulin and exercise during and after exercise, as well as the effects of regular exercise training on insulin action.

Saturated, but not n-6 polyunsaturated, fatty acids induce insulin resistance: role of intramuscular accumulation of lipid metabolites

2006 ◽  
Vol 100 (5) ◽  
pp. 1467-1474 ◽  
Author(s):  
Jong Sam Lee ◽  
Srijan K. Pinnamaneni ◽  
Su Ju Eo ◽  
In Ho Cho ◽  
Jae Hwan Pyo ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Insulin Sensitivity ◽  
Polyunsaturated Fatty Acids ◽  
Glucose Uptake ◽  
High Fat ◽  
Insulin Resistant ◽  
L6 Myotubes ◽  
Lipid Metabolites

Consumption of a Western diet rich in saturated fats is associated with obesity and insulin resistance. In some insulin-resistant phenotypes this is associated with accumulation of skeletal muscle fatty acids. We examined the effects of diets high in saturated fatty acids (Sat) or n-6 polyunsaturated fatty acids (PUFA) on skeletal muscle fatty acid metabolite accumulation and whole-body insulin sensitivity. Male Sprague-Dawley rats were fed a chow diet (16% calories from fat, Con) or a diet high (53%) in Sat or PUFA for 8 wk. Insulin sensitivity was assessed by fasting plasma glucose and insulin and glucose tolerance via an oral glucose tolerance test. Muscle ceramide and diacylglycerol (DAG) levels and triacylglycerol (TAG) fatty acids were also measured. Both high-fat diets increased plasma free fatty acid levels by 30%. Compared with Con, Sat-fed rats were insulin resistant, whereas PUFA-treated rats showed improved insulin sensitivity. Sat caused a 125% increase in muscle DAG and a small increase in TAG. Although PUFA also resulted in a small increase in DAG, the excess fatty acids were primarily directed toward TAG storage (105% above Con). Ceramide content was unaffected by either high-fat diet. To examine the effects of fatty acids on cellular lipid storage and glucose uptake in vitro, rat L6 myotubes were incubated for 5 h with saturated and polyunsaturated fatty acids. After treatment of L6 myotubes with palmitate (C16:0), the ceramide and DAG content were increased by two- and fivefold, respectively, concomitant with reduced insulin-stimulated glucose uptake. In contrast, treatment of these cells with linoleate (C18:2) did not alter DAG, ceramide levels, and glucose uptake compared with controls (no added fatty acids). Both 16:0 and 18:2 treatments increased myotube TAG levels (C18:2 vs. C16:0, P < 0.05). These results indicate that increasing dietary Sat induces insulin resistance with concomitant increases in muscle DAG. Diets rich in n-6 PUFA appear to prevent insulin resistance by directing fat into TAG, rather than other lipid metabolites.

scholarly journals Metabolic recovery of adipose tissue is associated with improvement in insulin resistance in a model of experimental diabetes

2008 ◽  
Vol 198 (1) ◽  
pp. 51-60 ◽  
Author(s):  
Julie Takada ◽  
Miriam Helena Fonseca-Alaniz ◽  
Tarcila Beatriz Ferraz de Campos ◽  
Sandra Andreotti ◽  
Amanda Baron Campana ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Energy Homeostasis ◽  
Hormone Secretion ◽  
Active Role ◽  
Metabolic Disturbances ◽  
Severe Insulin Resistance ◽  
Insulin Levels ◽  
Adipose Mass

Obesity and insulin resistance are highly correlated with metabolic disturbances. Both the excess and lack of adipose tissue can lead to severe insulin resistance and diabetes. Adipose tissue plays an active role in energy homeostasis, hormone secretion, and other proteins that affect insulin sensitivity, appetite, energy balance, and lipid metabolism. Rats with streptozotocin-induced diabetes during the neonatal period develop the classic diabetic picture of hyperglycemia, hypoinsulinemia, and insulin resistance in adulthood. Low body weight and reduced epididymal (EP) fat mass were also seen in this model. The aim of this study was to investigate the glucose homeostasis and metabolic repercussions on the adipose tissue following chronic treatment with antidiabetic drugs in these animals. In the 4th week post birth, diabetic animals started an 8-week treatment with pioglitazone, metformin, or insulin. Animals were then killed, EP fat pads were excised, and blood samples were collected for biological and biochemical assays. Pioglitazone and insulin treatments, but not metformin, reduced hyperglycemia, polydipsia, and polyphagia. Although all antidiabetic therapies improved insulin sensitivity, this was particularly noteworthy in the pioglitazone-treated rats. Furthermore, a recovery of adipose mass and insulin levels were observed in pioglitazone- and insulin-, but not metformin-treated animals. Treatments with insulin or pioglitazone were able to correct significantly, but not completely, the metabolic abnormalities, parallel to full recovery of adipose mass, indicating that not only the low insulin levels but also the lack of adipose tissue might play a significant role on the pathophysiology of this particular diabetes model.

Leptin, skeletal muscle lipids, and lipid-induced insulin resistance

2007 ◽  
Vol 293 (2) ◽  
pp. R642-R650 ◽  
Author(s):  
John J. Dube ◽  
Bankim A. Bhatt ◽  
Nikolas Dedousis ◽  
Arend Bonen ◽  
Robert M. O'Doherty
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Lipid Metabolism ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Glycogen Synthase ◽  
Acid Oxidation ◽  
Fatty Acid Binding ◽  
Lipid Metabolites

Leptin-induced increases in insulin sensitivity are well established and may be related to the effects of leptin on lipid metabolism. However, the effects of leptin on the levels of lipid metabolites implicated in pathogenesis of insulin resistance and the effects of leptin on lipid-induced insulin resistance are unknown. The current study addressed in rats the effects of hyperleptinemia (HL) on insulin action and markers of skeletal muscle (SkM) lipid metabolism in the absence or presence of acute hyperlipidemia induced by an infusion of a lipid emulsion. Compared with controls (CONT), HL increased insulin sensitivity, as assessed by hyperinsulinemic-euglycemic clamp (∼15%), and increased SkM Akt (∼30%) and glycogen synthase kinase 3α (∼52%) phosphorylation. These improvements in insulin action were associated with decreased SkM triglycerides (TG; ∼61%), elevated ceramides (∼50%), and similar diacylglycerol (DAG) levels in HL compared with CONT. Acute hyperlipidemia in CONT decreased insulin sensitivity (∼25%) and increased SkM DAG (∼33%) and ceramide (∼60%) levels. However, hyperlipidemia did not induce insulin resistance or SkM DAG and ceramide accumulation in HL. SkM total fatty acid transporter CD36, plasma membrane fatty acid binding protein, acetyl Co-A carboxylase phosphorylation, and fatty acid oxidation were similar in HL compared with CONT. However, HL decreased SkM protein kinase Cθ (PKCθ), a kinase implicated in mediating the detrimental effects of lipids on insulin action. We conclude that increases in insulin sensitivity induced by HL are associated with decreased levels of SkM TG and PKCθ and increased SkM insulin signaling, but not with decreases in other lipid metabolites implicated in altering SkM insulin sensitivity (DAG and ceramide). Furthermore, insulin resistance induced by an acute lipid infusion is prevented by HL.

scholarly journals Oleate Blocks Palmitate-Induced Abnormal Lipid Distribution, Endoplasmic Reticulum Expansion and Stress, and Insulin Resistance in Skeletal Muscle

Endocrinology ◽  
2011 ◽  
Vol 152 (6) ◽  
pp. 2206-2218 ◽  
Author(s):  
Gong Peng ◽  
Linghai Li ◽  
Yanbo Liu ◽  
Jing Pu ◽  
Shuyan Zhang ◽  
...  
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acids ◽  
Endoplasmic Reticulum ◽  
Insulin Sensitivity ◽  
Er Stress ◽  
Molecular Mechanisms ◽  
Dietary Fatty Acids ◽  
Akt Phosphorylation ◽  
Stress Relieving

Pathological elevation of plasma fatty acids reduces insulin sensitivity. Although several regulation pathways have been reported, the molecular mechanisms of insulin sensitivity remain elusive, especially in skeletal muscle where most glucose is consumed. This study focuses on how two major dietary fatty acids affect insulin signaling in skeletal muscle cells. Palmitic acid (PA) not only reduced insulin-stimulated phosphorylation of Akt but also induced endoplasmic reticulum (ER) expansion and ER stress. Relieving ER stress using 4-phenyl butyric acid blocked PA-mediated protein kinase R-like ER kinase phosphorylation and ER expansion and reversed the inhibitory effect of PA on insulin-stimulated Akt phosphorylation. Importantly, oleic acid (OA) could also recover PA-reduced Akt phosphorylation and abolish both PA-mediated ER expansion and ER stress. The competition between these two fatty acids was further verified in rat skeletal muscle using venous fatty acid infusion. 3H-labeled PA was converted mainly to active lipids (phospholipids and diacylglycerol) in the absence of OA, but to triacylglycerol in the presence of OA. Subcellular triacylglycerol and adipocyte differentiation-related protein from PA-treated cells cofractionated with the ER in the absence of OA but switched to the low-density fraction in the presence of OA. Taken together, these data suggest that the PA-mediated lipid composition and localization may cause ER expansion and consequently cause ER stress and insulin resistance in skeletal muscle.

scholarly journals Chronic renin inhibition with aliskiren improves glucose tolerance, insulin sensitivity, and skeletal muscle glucose transport activity in obese Zucker rats

2012 ◽  
Vol 302 (1) ◽  
pp. R137-R142 ◽  
Author(s):  
Elizabeth M. Marchionne ◽  
Maggie K. Diamond-Stanic ◽  
Mujalin Prasonnarong ◽  
Erik J. Henriksen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Insulin Sensitivity ◽  
Glucose Tolerance ◽  
Glucose Transport ◽  
Insulin Action ◽  
Whole Body ◽  
Zucker Rats ◽  
Obese Zucker Rats ◽  
Renin Inhibition

We have demonstrated previously that overactivity of the renin-angiotensin system (RAS) is associated with whole body and skeletal muscle insulin resistance in obese Zucker ( fa/fa) rats. Moreover, this obesity-associated insulin resistance is reduced by treatment with angiotensin-converting enzyme inhibitors or angiotensin receptor (type 1) blockers. However, it is currently unknown whether specific inhibition of renin itself, the rate-limiting step in RAS functionality, improves insulin action in obesity-associated insulin resistance. Therefore, the present study assessed the effect of chronic, selective renin inhibition using aliskiren on glucose tolerance, whole body insulin sensitivity, and insulin action on the glucose transport system in skeletal muscle of obese Zucker rats. Obese Zucker rats were treated for 21 days with either vehicle or aliskiren (50 mg/kg body wt ip). Renin inhibition was associated with a significant lowering (10%, P < 0.05) of resting systolic blood pressure and induced reductions in fasting plasma glucose (11%) and free fatty acids (46%) and homeostatic model assessment for insulin resistance (13%). Glucose tolerance (glucose area under the curve) and whole body insulin sensitivity (inverse of the glucose-insulin index) during an oral glucose tolerance test were improved by 15% and 16%, respectively, following chronic renin inhibition. Moreover, insulin-stimulated glucose transport activity in isolated soleus muscle of renin inhibitor-treated animals was increased by 36% and was associated with a 2.2-fold greater Akt Ser473 phosphorylation. These data provide evidence that chronic selective inhibition of renin activity leads to improvements in glucose tolerance and whole body insulin sensitivity in the insulin-resistant obese Zucker rat. Importantly, chronic renin inhibition is associated with upregulation of insulin action on skeletal muscle glucose transport, and it may involve improved Akt signaling. These data support the strategy of targeting the RAS to improve both blood pressure regulation and insulin action in conditions of insulin resistance.

scholarly journals Peroxisome Proliferator-Activated Receptor (PPAR) Activation Induces Tissue-Specific Effects on Fatty Acid Uptake and Metabolism in Vivo—A Study Using the Novel PPARα/γ Agonist Tesaglitazar

Endocrinology ◽  
2004 ◽  
Vol 145 (7) ◽  
pp. 3158-3164 ◽  
Author(s):  
Bronwyn D. Hegarty ◽  
Stuart M. Furler ◽  
Nicholas D. Oakes ◽  
Edward W. Kraegen ◽  
Gregory J. Cooney
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Fatty Acid ◽  
Insulin Sensitivity ◽  
Insulin Action ◽  
Whole Body ◽  
Peroxisome Proliferator ◽  
The Novel ◽  
High Fat

Abstract Agonists of peroxisome proliferator-activated receptors (PPARs) have emerged as important pharmacological agents for improving insulin action. A major mechanism of action of PPAR agonists is thought to involve the alteration of the tissue distribution of nonesterified fatty acid (NEFA) uptake and utilization. To test this hypothesis directly, we examined the effect of the novel PPARα/γ agonist tesaglitazar on whole-body insulin sensitivity and NEFA clearance into epididymal white adipose tissue (WAT), red gastrocnemius muscle, and liver in rats with dietary-induced insulin resistance. Wistar rats were fed a high-fat diet (59% of calories as fat) for 3 wk with or without treatment with tesaglitazar (1 μmol·kg−1·d−1, 7 d). NEFA clearance was measured using the partially metabolizable NEFA tracer, 3H-R-bromopalmitate, administered under conditions of basal or elevated NEFA availability. Tesaglitazar improved the insulin sensitivity of high-fat-fed rats, indicated by an increase in the glucose infusion rate during hyperinsulinemic-euglycemic clamp (P &lt; 0.01). This improvement in insulin action was associated with decreased diglyceride (P &lt; 0.05) and long chain acyl coenzyme A (P &lt; 0.05) in skeletal muscle. NEFA clearance into WAT of high-fat-fed rats was increased 52% by tesaglitazar under basal conditions (P &lt; 0.001). In addition the PPARα/γ agonist moderately increased hepatic and muscle NEFA utilization and reduced hepatic triglyceride accumulation (P &lt; 0.05). This study shows that tesaglitazar is an effective insulin-sensitizing agent in a mild dietary model of insulin resistance. Furthermore, we provide the first direct in vivo evidence that an agonist of both PPARα and PPARγ increases the ability of WAT, liver, and skeletal muscle to use fatty acids in association with its beneficial effects on insulin action in this model.

scholarly journals Early postnatal oestradiol exposure causes insulin resistance and signs of inflammation in circulation and skeletal muscle

2009 ◽  
Vol 201 (1) ◽  
pp. 49-58 ◽  
Author(s):  
Camilla Alexanderson ◽  
Elias Eriksson ◽  
Elisabet Stener-Victorin ◽  
Malin Lönn ◽  
Agneta Holmäng
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Uncoupling Protein ◽  
Female Rats ◽  
Whole Body ◽  
Low Grade ◽  
Expression Of Genes ◽  
Genes Encoding

Early postnatal events can predispose to metabolic and endocrine disease in adulthood. In this study, we evaluated the programming effects of a single early postnatal oestradiol injection on insulin sensitivity in adult female rats. We also assessed the expression of genes involved in inflammation and glucose metabolism in skeletal muscle and adipose tissue and analysed circulating inflammation markers as possible mediators of insulin resistance. Neonatal oestradiol exposure reduced insulin sensitivity and increased plasma levels of monocyte chemoattractant protein-1 (MCP-1) and soluble intercellular adhesion molecule-1. In skeletal muscle, oestradiol increased the expression of genes encoding complement component 3 (C3), Mcp-1, retinol binding protein-4 (Rbp4) and transforming growth factor β1 (Tgfβ1). C3 and MCP-1 are both related to insulin resistance, and C3, MCP-1 and TGFβ1 are also involved in inflammation. Expression of genes encoding glucose transporter-4 (Glut 4), carnitine-palmitoyl transferase 1b (Cpt1b), peroxisome proliferator-activated receptor δ (Ppard) and uncoupling protein 3 (Ucp3), which are connected to glucose uptake, lipid oxidation, and energy uncoupling, was down regulated. Expression of several inflammatory genes in skeletal muscle correlated negatively with whole-body insulin sensitivity. In s.c. inguinal adipose tissue, expression of Tgfβ1, Ppard and C3 was decreased, while expression of Rbp4 and Cpt1b was increased. Inguinal adipose tissue weight was increased but adipocyte size was unaltered, suggesting an increased number of adipocytes. We suggest that early neonatal oestrogen exposure may reduce insulin sensitivity by inducing chronic, low-grade systemic and skeletal muscle inflammation and disturbances of glucose and lipid metabolism in skeletal muscle in adulthood.

scholarly journals The effects of obesity-associated insulin resistance on mRNA expression of peroxisome proliferator-activated receptor-γ target genes, in dogs

2007 ◽  
Vol 98 (3) ◽  
pp. 497-503 ◽  
Author(s):  
Constance Gayet ◽  
Veronique Leray ◽  
Masayuki Saito ◽  
Brigitte Siliart ◽  
Patrick Nguyen
Keyword(s):  
Insulin Resistance ◽  
Skeletal Muscle ◽  
Adipose Tissue ◽  
Insulin Sensitivity ◽  
Mrna Expression ◽  
Target Genes ◽  
Peroxisome Proliferator ◽  
Peroxisome Proliferator Activated Receptor ◽  
Glucose And Lipid Metabolism ◽  
Visceral Adipose

Visceral adipose tissue and skeletal muscle have central roles in determining whole-body insulin sensitivity. The peroxisome proliferator-activated receptor-γ (PPARγ) is a potential mediator of insulin sensitivity. It can directly modulate the expression of genes that are involved in glucose and lipid metabolism, including GLUT4, lipoprotein lipase (LPL) and adipocytokines (leptin and adiponectin). In this study, we aimed to determine the effects of obesity-associated insulin resistance on mRNA expression of PPARγ and its target genes. Dogs were studied when they were lean and at the end of an overfeeding period when they had reached a steady obese state. The use of a sensitive, real-time PCR assay allowed a relative quantification of mRNA expression for PPARγ, LPL, GLUT4, leptin and adiponectin, in adipose tissue and skeletal muscle. In visceral adipose tissue and/or skeletal muscle, mRNA expression of PPARγ, LPL and GLUT4 were at least 2-fold less in obese and insulin-resistant dogs compared with the same animals when they were lean and insulin-sensitive. The mRNA expression and plasma concentration of leptin was increased, whereas the plasma level and mRNA expression of adiponectin was decreased, by obesity. In adipose tissue, PPARγ expression was correlated with leptin and adiponectin. These findings, in an original model of obesity induced by a prolonged period of overfeeding, showed that insulin resistance is associated with a decrease in PPARγ mRNA expression that could dysregulate expression of several genes involved in glucose and lipid metabolism.

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