Serum levels of appetite-regulating hormones and pro-inflammatory cytokines are ameliorated by a CLA diet and endurance exercise in rats fed a high-fat diet

Article information

J Exerc Nutrition Biochem. 2015;19(4):303-309
Institute of Sports Health Science, Sunmoon University, Chung Nam Republic of Korea
*Youngju Song, Tel. 82-41-530-2239, Email.
Received 2015 October 19; Revised 2015 December 03; Accepted 2015 December 09.



This study examined whether conjugated linoleic acid (CLA) supplementation and endurance exercise affect appetite-regulating hormones and pro-inflammatory cytokines in rats.


Seven-week-old male Sprague-Dawley rats were divided randomly into the high-fat diet sedentary group (HS, n=8), the 1.0% CLA supplemented high-fat diet sedentary group (CS, n=8), and the 1.0% CLA supplemented high-fat diet exercise group (CE, n=8). Rats in the CE group swam 60 min/day, 5 days/week for 4 weeks.


Leptin and insulin levels in the CS and CE groups were significantly lower than those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels decreased significantly in the CE compared to those in the CS group. Interleukin (IL)-1β (p<0.001) and IL-6 (p<0.01) levels in the CS and CE groups decreased significantly compared to those in the HS group. Leptin (IL-1β: r=0.835, p<0.001), IL-6 (r=0.607, p<0.05), insulin (IL-1β: r=0.797, p<0.01), and IL-6 (r=0.827, p<0.01) levels were positively related with pro-inflammatory cytokine levels.


Endurance exercise may play an important role during CLA supplementation of rats on a high-fat diet.


Regular exercise results in physiological adaptations that benefit almost every organ system in the body to improve overall health. Endurance exercise has long been reported to decrease obesity, ameliorate the postprandial triglyceridemic response, increase the fat oxidation rate, and improve insulin sensitivity [1-4].

Conjugated linoleic acid (CLA) is an important food component that consists of a mixture of positional and geometric isomers of linoleic acid (cis-9, cis-12, and C18:2) with two conjugated double bonds at various carbon positions in the fatty acid chain [5]. A mixed CLA isomer is commercially marketed as a weight-loss supplement. Although CLA is considered an alternative medicine with minimal side effects compared with mainstream anti-obesity drugs, it has been reported to induce upset stomach, nausea, and loose stools because of its lack of absorption and instability [6,7]. CLA is also considered an important biologically-active compound in food due to its proven anti-carcinogenic, anti-allergic, and anti-inflammatory properties [8-10]. Feeding studies in animals have suggested that a 0.4-2.0% CLA mixture [5-10] can be used to determine the effect of a mixed CLA isomer. Based on these studies, was used a 1.0% CLA mixture as a supplement in this study.

Leptin and insulin levels increase as a result of obesity [11]. Leptin exerts central effects on hypothalamic-pituitary function and markedly regulates appetite, thermogenesis, and food intake [12]. Dietary intake and body weight are challenged by the fact that the majority of obese people exhibit high levels of circulating leptin, to which they are apparently resistant [13]. Insulin is released from the pancreas and leptin is released from adipose tissue, and these hormones help regulate long-term energy balance [14]. Recent experimental data suggest that leptin can act directly on the liver to influence the insulin and leptin signaling pathways [15].

Adipose tissue is active, and secretes proteins, such as leptin, interleukin (IL)-6, IL-8, and tumor necrosis factor (TNF)-α, which play key roles regulating cellular and humoral immune responses to malignancies [16,17]. An increase in IL-6 level combined with detectable levels of IL-1β result in a significantly elevated risk for developing type 2 diabetes that is not observed when either cytokine alone is detected at a higher level [18]. IL-1β has similar actions to those of IL-6 and TNF-α, and IL-1β and TNF-α are potent inducers of IL-6 production and activity. In contrast, IL-6 may inhibit IL-1β and TNF-α production and inhibit TNF-mediated monocyte cytotoxicity to tumor target cells [19].

CLA is considered a weight-loss supplement, and endurance exercise decreases the frequency of obesity. Therefore, we compared the effects of endurance exercise on the levels of appetite-regulating hormones, such as leptin and insulin, as well as pro-inflammatory cytokines in rats supplemented with 1.0% CLA.


Experimental animals and dietary intake measurement

Six-week-old male Sprague-Dawley rats (weight, 230-250 g) were obtained (Samtako Co., Osan, Korea) and housed individually in a controlled environment of 23±1°C, 50±5% relative humidity, and a 12 hour light-dark cycle. All animals were given free access to tap water and food. After the 1-week acclimation period, the rats were divided randomly into three groups: HS, high-fat diet (HFD) (35% fat of total diet weight) [20] sedentary; CS, CLA supplemented HFD sedentary group; and CE, CLA supplemented HFD exercise group. CLA (1.0% of a 76.82% CLA mixture; 36.8% cis-9,trans-11 CLA, 37.8% trans-10,cis-12 CLA, and 1.2% trans-9,trans-11 CLA) (HK Biotech Co., Gyeongnam, Korea) was substituted for the dietary fat in the adjusted HFD (Table 1). Food intake was measured daily, and the change in body weight of each animal was noted weekly. The diets were modified from a previous study [20] and based on AIN-76G. The food efficiency ratio was calculated as total weight gain divided by total food intake for the experimental period. All experimental protocols were approved by the Animal Study Committee of Sunmoon University.

Composition of the experimental diets

Exercise protocol and sample collection

The exercised rats swam (50-60% VO2max) 60 min/day, 5 days/week for 4 weeks [2,21]. Water temperature in the plastic barrel (depth, 50 cm and radius, 25 cm) swimming pool was maintained at 35±1°C [22]. At the end of the experiment, the 12-hour overnight-fasted rats were sacrificed by exsanguination, and blood was withdrawn from the left ventricle under light diethyl ether anesthesia. Serum, liver, gastrocnemius muscle, and perirenal fat were dissected and immediately snap-frozen in liquid nitrogen. The organs and tissue were stored at -70°C until analyses.

Biochemical assays

Fasting serum insulin levels were measured using standard radioimmunoassay kits (Linco Research, Inc., St. Louis, MO, USA). Serum leptin, IL-1β, and IL-6 levels were analyzed using quantitative sandwich enzyme immunoassay kits (R & D Systems, San Diego, CA, USA). The lower limit of detection was 3.13 pg/ml. Values below this limit were assumed to be zero for the statistical analysis. The inter- and intra-assay coefficients of variation were <10%.

Statistical analysis

Data are expressed as mean±standard error using the SPSS/PC ver. 18.0 software program for Windows (SPSS Inc., Chicago, IL, USA). All statistical analyses were conducted using one-way analysis of variance followed by the least significant difference post-hoc test. Linear relationships between leptin and insulin levels and IL-1β and IL-6 levels were examined using Pearson’s correlation analysis. A p<0.05 was considered significant.


Changes in the body composition-related variables

The changes in body composition-related variables are summarized in Table 2. Total body weight and cumulative body weight gain in the CS and CE groups decreased significantly compared to those in the HS group (p<0.001). Liver and perirenal fat weights in the CS (p<0.05) and CE (p<0.01) groups decreased significantly compared to those in the HS group. However, gastrocnemius muscle weight was not different among the groups.

Body composition-related variables

Changes in appetite-related variables

Serum leptin and insulin levels in the CS and CE groups decreased significantly relative to those in the HS group (p<0.001), whereas leptin (p<0.01) and insulin (p<0.05) levels in the CE group decreased significantly compared to those in the CS group (Table 3). Food intake amounts by the CS and CE groups were significantly lower than that by the HS group (p<0.001). The food efficiency ratio values of the CS (p<0.001) and CE (p<0.001) groups were lower than that of the HS group, whereas the food efficiency ratio of the CE group decreased significantly (p<0.01).

Appetite-related variables

Changes in pro-inflammatory cytokines

Changes in the pro-inflammatory cytokines IL-1β and IL-6 are presented in Table 4. IL-1β levels in the CS and CE groups decreased significantly compare to those in the HS group (p<0.001). In addition, IL-6 levels in the CS and CE groups were significantly lower than those in the CS group (p<0.01).

Pro-inflammatory cytokines

Linear relationships between leptin and insulin and the pro-inflammatory cytokines

The levels of leptin and the pro-inflammatory cytokines (IL-1β: r=0.835, p<0.001 and IL-6: r=0.607, p<0.05) were positively correlated (Fig. 1). Additionally, highly significant positive correlations were detected between levels of insulin and the pro-inflammatory cytokines (IL-1β: r=0.797, p<0.01 and IL-6: r=0.827, p<0.01).

Fig. 1.

Linear relationships between the appetite-regulating hormones and pro-inflammatory cytokines


The results of this study show that the CLA diet and endurance exercise were positively associated with the levels of insulin, leptin, and pro-inflammatory cytokines, such as IL-1β and IL-6, in rats fed a high-fat diet.

Endurance exercise enhances weight loss because it lowers the energetic balance by increasing energy expenditure and reducing food intake [1-3]. Haghshenas et al [14] reported that increased energy intake is likely to result from changes in the appetite control system toward an anorexigenic environment. Our findings agree with studies reported previously, showing that regular participation in endurance exercise decreases body and fat mass [23,24].

The most pronounced effect of supplementation with the CLA isomer is stimulation of protein synthesis, which reduces body mass and fat mass [25-30]. Previous studies showed that CLA reduced adiposity in experimental animals, including mice, rats, and pigs [5-10]. These animal studies demonstrate that total fat mass decreased >50% in animals fed a diet containing a 1.0% CLA mixture compared to those fed a control diet (without CLA). Thus, we used 1.0% CLA in an AIN-76-based diet in the present study. As mentioned previously, CLA is marketed as a weight-loss supplement. Our results are consistent with results of previous studies. The rat groups supplemented with CLA with/without endurance exercise tended to have lower cumulative body weight gain and fat pad weight. Thus, our results show that 1.0% CLA supplementation may reduce body and fat weight regardless of endurance exercise while eating a high-fat diet.

Some scholars have considered leptin to be a warning mechanism for adjusting the body’s fat content [31]. Alessia et al. [32] reported that dietary CLA supplementation decreases leptin in porcine adipose tissue, and they hypothesize an increase in noradrenergic stimulation of lipolysis directly in target tissue. Other studies have reported that regular endurance exercise ameliorates serum leptin levels [33]. An impaired hypothalamic insulin signaling pathways is sufficient to promote obesity and type 2 diabetes in different genetic rodent models in which insulin signaling was neuronally ablated [12,14,15]. In our study, insulin levels decreased in the CS and CE groups compared to those in HFD and sedentary groups. These findings show that a CLA-supplemented diet decreased insulin level, but endurance exercise had no effect. Some studies have reported that CLA is inversely associated with serum insulin and leptin levels [34-39]. They assumed that a decrease in insulin concentration suggested that CLA supplementation enhanced insulin sensitivity. Our results were in line with those reports. In our results, insulin and leptin, which are appetite-regulating hormones, showed synergistic effects during endurance exercise, suggesting that endurance exercise could potentially lower leptin and insulin resistance during CLA supplementation. Therefore, combining endurance exercise and CLA supplementation may improve leptin and insulin levels compared to those of CLA supplementation alone, even in rats fed HFD.

Some studies have demonstrated that endurance exercise inhibits release of the inflammatory mediators IL-1β, IL-6, and TNF-α from fat tissues by decreasing the stimulation of the sympathetic system and increasing production of anti- inflammatory cytokines [40-42]. Those reports have described that human leptin stimulates the production of cytokines, such as TNF-α and IL-6. In the present study, we found significant improvement between serum leptin levels and inflammatory markers such as IL-1β and IL-6. Our observation suggests that combining CLA supplementation and endurance exercise may help improve leptin level by controlling pro-inflammatory cytokines, such as IL-1B and IL-6, in adolescent rats fed a HFD.

Leptin and insulin secretion are regulated by inflammatory mediators and exert central effects on hypothalamic-pituitary function [14]. IL-1 and TNF-α have been implicated in the regulation of leptin secretion where they induce production of leptin from adipocytes [43,44]. In addition, Takács et al. reported that human leptin stimulates production of cytokines, such as TNF-α and IL-6 [45]. Our results agree with previous studies that increased leptin and insulin concentrations might lead to increased IL-1β and IL-6 concentrations. Although, there was no synergistic effect of the CLA diet and endurance exercise on IL-1β and IL-6 levels, the appetite-regulating hormones and pro-inflammatory cytokines were significantly positively correlated with IL-1β and IL-6 in our results, suggesting that the leptin and insulin induced by CLA and endurance exercise in rats fed a HFD stimulated production of pro-inflammatory cytokines, such as IL-1β and IL-6.

As mentioned above, combining CLA supplementation and endurance exercise tended to result in lower obesity indices and improved of appetite-regulating hormone and pro-inflammatory cytokine levels than CLA supplementation or endurance exercise alone. We did not test the effect of exercise on the HFD group. Thus, we cannot explain the effect of exercise without CLA supplementation, which is a limitation.

In conclusion, endurance exercise may play a beneficial role with CLA supplementation in rats on a HFD to improve levels of appetite-regulating hormones and pro-inflammatory cytokines.


1. Calegari VC., Zoppi CC., Rezende LF., Siverira LR., Cameiro EM., Boschero AC.. Endurance training activates AMP-activated protein kinase, increases expression of uncoupling protein 2 and reduces insulin secretion form rat pancreatic islets. J Endocrinol 2011;208:257–64. 21212094.
2. Hung YH., Linden MA., Gordon A., Rector RS., Buhman KK.. Endurance exercise training programs intestinal lipid metabolism in a rat model of obesity and type 2 diabetes. Physiol Rep 2015;3e12232th ed. 10.14814/phy2.12232.
3. Goodyear LJ., Kahn BB.. Exercise, glucose transport, and insulin sensitivity. Annu Rev Med 1998;49:235–61. 10.1146/ 9509261.
4. Holland AM., Hyatt HW., Smuder AJ., Sollanek KJ., Morton AB., Roberts MD., Kavazis AN.. Influence of endurance exercise training on antioxidant enzymes, tight junction proteins, and inflammatory markers in the rat ileum. BMC Res Notes 2015;8:514–23. 10.1186/s13104-015-1500-6. 26423686.
5. Moon HS., Lee HG., Seo JH., Chung CS., Kim TG., Choi YJ., Cho CS.. Antiobesity effect of PEGylated conjugated linoleic acid on high-fat diet induced obese C57BL/6J (ob/ob) mice; attenuation of insulin resistance and enhancement of antioxidant defenses. J Nutr Biochem 2009;20:187–94. 10.1016/j.jnutbio.2008.02.001. 18602810.
6. Gonçalves DC., Lira FS., Carnevali LC. Jr, Rosa JC., Pimentel GD., Seelaender M.. Conjugated linoleic acid: good or bad nutrient. Diabetol Metab Syndr 2010;2:62–73. 10.1186/1758-5996-2-62. 21034495.
7. Azain MJ., Hausman DB., Sisk MB., Flatt WP., Jewell DE.. Dietary conjugated linoleic acid reduces fat adipose tissue cell size rather than cell number. J Nutr 2000;130:1548–54. 10827208.
8. Wendel AA., Purushotham A., Liu LF., Belury MA.. Conjugated linoleic acid fails to worsen insulin resistance but induces hepatic steatosis in the presence of leptin in ob/ob mice. J Lipid Res 2008;49:98–106. 10.1194/jlr.M700195-JLR200. 17906221.
9. DeLany JP., Blohm F., Truett AA., Scimeca J., West DB.. Conjugated linoleic acid reduces body fat content in mice without affecting energy intake. Am J Physiol 1999;276:R1172–9. 10198400.
10. Park Y., Albright KJ., Liu W., Storkson JM., Cook ME., Pariza MW.. Effect of conjugated linoleic acid on body composition in mice. Lipids 1997;32:853–8. 10.1007/s11745-997-0109-x. 9270977.
11. Cadena-Schlam L., López-Guimerà G.. Intuitive eating: an emerging approach to eating behavior. Nutr Hosp 2014;31:995–1002. 25726186.
12. Stensel D.. Exercise, appetite and appetite-regulation hormones: implications for food intake and weight control. Ann Nutr Metab 2010;57:36–42. 10.1159/000322702. 21346335.
13. Schrauwen P., Westerterp KR.. The role of high-fat diet and physical activity in the regulation of body weight. Br J Nutr 2000;84:417–27. 10.1017/S0007114500001720. 11103212.
14. Haghshenas R., Jafari M., Ravasi A., Kordi M., Gilani N., Shariatzadeh M., Hedayati M., Rahimi M.. The effect of eight weeks endurance training and high-fat diet on appetite-regulating hormones in rat plasma. Iran J Basic Med Sci 2014;17:237–43. 24904715.
15. Ropelle ER., Flores MB., Cintra DE., Rocha GZ., Pauli JR., Morari J., de Souza CT., Moraes JC., Prada PO., Guadagnini D., Marin RM., Oliveira AG., Augusto TM., Carvalho HF., Velloso LA., Saad MJ., Carvalheira JB.. IL-6 and IL-10 antiflammatory activity links exercise to hypothalamic insulin and leptin sensitivity through IKKB and ER stress inhibition. PLoS Biol 2010;8e1000465th ed. 10.1371/journal.pbio.1000465.
16. Strober W., Fuss IJ.. Proinflammatory cytokines in the pathogenesis of inflammatory bowel disease. Gastroenterology 2011;140:1756–67. 10.1053/j.gastro.2011.02.016. 21530742.
17. Cosnes J., Gower-Rousseau C., Seksik P., Cortot A.. Epidemiology and natural history of inflammatory bowel diseases. Gastroenterlogy 2001;140:1785–94. 10.1053/j.gastro.2011.01.055.
18. O'Neill CM., Lu C., Corbin KL., Sharma PR., Dula SB., Carter JD., Ramadan JW., Xin W., Lee JK.. Nunemaker CS. Circulating levels of IL-1β+IL-6 causes ER stress and dysfunction in islets from prediabetic male mice. Endocrinology 2013;154:3077–88. 10.1210/en.2012-2138. 23836031.
19. Jablonska E., Piotrowski L., Grabowska Z.. Serum levels of IL-1b, IL-6, TNF-a, sTNF-RI and CRP in patients with oral cavity cancer. Pathol Oncol Res 1997;3:126–9. 10.1007/BF02907807. 11173639.
20. Hariri N., Thibault L.. High-fat diet induced obesity in animal models. Nutr Res Rev 2010;23:270–99. 10.1017/S0954422410000168. 20977819.
21. Oztasan N., Taysi S., Gumustekin K., Altinkaynak K., Aktas O., Timur H., Siktar E., Keles S., Akar S., Akcay F., Dane S., Gul M.. Endurance training attenuates exercise-induced oxidative stress in erythrocytes in rat. Eur J Appl Physiol 2004;91:622–7. 10.1007/s00421-003-1029-6. 14685869.
22. Kwon DK., Hwang KH., Kim YK., Lee KH., Song YJ.. Effects of swimming exercise and soybean supplementation on the immune functions of rats fed a high fat diet. Clin Exp Pharmacol Physiol 2008;35:638–42. 10.1111/j.1440-1681.2007.04847.x. 18177482.
23. Kim CH., Youn JH., Park JY., Hong SK., Park KS., Park SW., Suh KI., Lee KU.. Effects of high-fat diet and exercise training on intracellular glucose metabolism in rats. Am J Physiol Endocrinol Metab 2000;278:E977–84. 10826998.
24. Sanal E., Ardic F., Kirac S.. Effects of aerobic or combined aerobic resistance exercise on body composition in overweight and obese adults: gender differences. A randomized intervention study. Eur J Phys Rehabil Med 2013;49:1–11. 22569489.
25. Koba K., Akahoshi A., Yamasaki M., Tanaka K., Yamada K., Iwata T., Kamegai T., Tsutsumi K., Sugano M.. Dietary conjugated linoleic acid in relation to CLA differently modifies body fat mass and serum and liver lipid levels in rats. Lipids 2002;37:343–50. 10.1007/s11745-002-0901-7. 12030314.
26. Poulos SP., Sisk M., Hausman DB., Azain MJ., Hausman GJ.. Pre- and postnatal dietary conjugated linoleic acid alters adipose development, body weight gain and body composition in Sprague-Dawley rats. J Nutr 2001;131:2722–31. 11584096.
27. Yamasaki M., Ikeda A., Oji M., Tanaka Y., Hirao A., Kasai M., Iwata T., Tachibana H., Yamada K.. Modulation of body fat and serum leptin levels by dietary conjugated linoleic acid in Sprague Dawley rats fed various fat-level diets. Nutrition 2003;19:30–5. 10.1016/S0899-9007(02)00842-0. 12507636.
28. Patureau Mirand P., Mosoni L., Arnal-Bagnard MA., Faulconnier Y., Chardigny JM., Chilliard Y.. Dietary conjugated linoleic acid has limited effects on tissue protein anabolism in sedentary and exercising adult rats. Reprod Nutr Dev 2006;46:621–32. 10.1051/rnd:2006040. 17169309.
29. Park Y., Albright KJ., Storkson JM., Liu W., Cook ME., Pariza MW.. Changes in body composition in mice during feeding and withdrawal of conjugated linoleic acid. Lipids 1999;34:243–8. 10.1007/s11745-999-0359-7. 10230717.
30. Patureau Mirand P., Mosoni L., Arnal-Bagnard MA., Faulconnier Y., Chardigny JM., Chilliard Y.. Dietary conjugated linoleic acid has limited effects on tissue protein anabolism in sedentary and exercising adult rats. Reprod Nutr Dev 2006;46:621–32. 10.1051/rnd:2006040. 17169309.
31. Izadi V., Saraf-Bank S., Azadbakht L.. Dietary intakes and leptin concentration. ARYA Atheroscler 2014;10:266–72. 25477984.
32. Di Giancamillo A., Rossi R., Vitari F., Pastorelli G., Corino C., Domeneghini C.. Dietary conjugated linoleic acid decreases leptin in porcine adipose tissue. J Nutr 2009;139:1867–72. 10.3945/jn.109.110627. 19710164.
33. Zhao J., Tian Y., Xu J., Liu D., Wang X., Zhao B.. Endurance exercise is a leptin signaling mimetic in hypothalamus of Wistar rats. Lipids Health Dis 2011;10:225–32. 10.1186/1476-511X-10-225. 22136466.
34. Sarigianni M., Bekiari E., Tsapas A., Kaloyianni M., Koliakos G., Paletas K.. Effect of leptin and insulin resistance on properties of human monocytes in lean and obese healthy participants. Angiologoy 2010;61:768–74. 10.1177/0003319710369104.
35. Kennedy A., Martinez K., Schmidt S., Mandrup S., LaPoint K., Mcintosh M.. Antiobesity mechanisms of action of conjugated linoleic acid. J Nutr Biochem 2010;21:171–9. 10.1016/j.jnutbio.2009.08.003. 19954947.
36. Altirriba J., Poher AL., Rohner-Jeanrenaud F.. Chronic oxytocin administration as a treatment against impaired leptin signaling or leptin resistance in obesity. Front Endocrinol (Lausanne) 2015;6:119. 10.3389/fendo.2015.00119. 26300847.
37. Rubin D., Herrmann J., Much D., Pfeuffer M., Laue C., Winkler P., Helwig U., Bell D., Auinger A., Darabaneanu S., Ruether A., Schrezenmeir J.. Influence of different CLA isomers on insulin resistance and adipocytokines in pre-diabetic, middle-aged men with PPARγ2 Pro12Ala polymorphism. Genes Nutr 2012;7:499–509. 10.1007/s12263-012-0289-3. 22399314.
38. Choi JD., Koh IU., Jung MH., Song J.. Effects of three different conjugated linoleic acid preparations on insulin signaling, fat oxidation and mitochondrial function in rats fed a high-fat diet. Br J Nutr 2007;98:264–75. 10.1017/S000711450770497X. 17408517.
39. Gudbrandsen OA., Rodríguez E., Wergedahl H., Mørk S., Reseland JE., Skorve J., Palou A., Berge RK.. Trans-10, cis-12-conjugated linoleic acid reduces the hepatic triacylglycerol content and the leptin mRNA level in adipose tissue in obese Zucker fa/fa rats. Br J Nutr 2009;102:803–15. 10.1017/S0007114509297200. 19298684.
40. Bezpalko L., Gavrilyuk O., Zayachkivska O.. Inflammatory response in visceral fat tissue and liver is prenatally programmed: experimental research. J Physiol Pharmacol 2015;66:57–64. 25716965.
41. Jitprasertwong P., Jaedicke KM., Nile CJ., Preshaw PM., Taylor JJ.. Leptin enhances the secretion of interleukin (IL)-18, but not IL-1β, from human monocytes via activation of caspase-1. Cytokine 2014;65:222–30. 10.1016/j.cyto.2013.10.008. 24275551.
42. Burke SJ., Stadler K., Lu D., Gleason E., Han A., Donohoe DR., Rogers RC., Hermann GE., Karlstad MD., Collier JJ.. IL-1β reciprocally regulates chemokine and insulin secretion in pancreatic β-cells via NF-κB. Am J Physiol Endocrinol Metab 2015;309:E715–26. 10.1152/ajpendo.00153.2015. 26306596.
43. Rao YQ., Li J., Wang WJ.. Effects of Gengnianchun on learning and memory ability, neurotransmitter, cytokines, and leptin in ovariectomized rats. Int J Clin Exp Med 2015;8:8648–60. 26309517.
44. Boonloh K., Kukongviriyapan V., Kongyingyoes B., Kukongviriyapan U., Thawornchinsombut S., Pannangpetch P.. Rice bran protein hydrolysates improve insulin resistance and decrease pro-inflammatory cytokine gene expression in rats fed a high carbohydrate-high fat diet. Nutrients 2015;7:6313–29. 10.3390/nu7085292. 26247962.
45. Takács G., Szalay C., Nagy B., Szabó I., Simon D., Berki T., Karádi Z.. Insulin and leptin plasma levels after the microinjection of interleukin-1β into the nucleus accumbens of the rat. Acta Physiol Hung 2012;99:472–8. 10.1556/APhysiol.99.2012.4.11. 23238549.

Article information Continued

Table 1.

Composition of the experimental diets

Variable High-fat diet1) CLA Suppl. diet2)
Ingredients (g/kg diet)
Casein 200.0 200.0
Starch 200.0 200.0
Sucrose 150.0 150.0
Lard 350.0 337.0
Cellulose 50.0 50.0
Mineral mix 35.0 35.0
Vitamin mix 10.0 10.0
DL-methionine 3.0 3.0
Choline barbiturate 2.0 2.0
DL-a-tocopherol 1.2 1.2
c-9, t-11 CLA3) - 6.5
t-10, c-12 CLA3) - 6.5
Energy (kcal/kg) 5350.0 5350.0
Protein (% kcal/g) 15.0 15.0
Carbohydrate (% kcal/g) 26.0 26.0
Fat (% kcal/g) 59.0 59.0

1)The high-fat diet (HFD) sedentary (HS) group received 35% fat of total diet weight

2)The conjugated linoleic acid (CLA) supplemented HFD sedentary (CS) and 1.0% CLA supplemented HFD exercise (CE) groups received 1.0% CLA in the HFD

3)76.81% CLA mixture

Table 2.

Body composition-related variables

Variable (g) HS (n=8) CS (n=8) CE (n=8)
Body weight 467.9±3.3 432.0±5.6*** 415.2±5.5***
Cumulative body weight gain 198.1±3.2 159.8±3.1*** 144.2±2.9***
Liver 11.9±0.2 10.5±0.3* 10.2±0.3**
Gastrocnemius muscle 1.909±0.043 1.930±0.074 1.995±0.039
Perirenal fat pad 16.1±1.1 13.3±1.4* 11.1±0.6**

Data are mean±standard error.

*p<0.05, **p<0.01, and ***p<0.001 compared with the high-fat diet (HFD) sedentary (HS) group.

##p<0.01 compared with the conjugated linoleic acid supplemented HFD sedentary (CS) group.

Table 3.

Appetite-related variables

Variable HS (n=8) CS (n=8) CE (n=8)
Hormonal variables
Leptin (ng/mL) 21.4±0.7 12.7±0.6*** 7.8±0.5***,##
Insulin (ng/mL) 4.9±0.5 3.0±0.3*** 1.7±0.4***,#
Food intake variables
Food intake amount (g) 381.8±3.1 340.8±3.8*** 338.8±7.1***
Food efficiency ratio 0.216±0.008 0.163±0.005*** 0.119±0.145***,##

Data are mean±standard error.

***p<0.001 compared with the high-fat diet (HFD) sedentary (HS) group.

#p<0.05, ##p<0.01 compared with the conjugated linoleic acid supplemented HFD sedentary (CS) group.

Table 4.

Pro-inflammatory cytokines

Variable HS (n=8) CS (n=8) CE (n=8)
Interleukin-1β (pg/mL) 44.7±1.0 39.0±0.7*** 37.4±0.5***
Interleukin-6 (pg/mL) 63.6±3.9 50.6±1.3** 49.3±2.5**

Data are mean±standard error.

**p<0.01 and ***p<0.001 compared with the high-fat diet sedentary (HS) group.

Fig. 1.

Linear relationships between the appetite-regulating hormones and pro-inflammatory cytokines