Intermuscular and intramuscular adipose tissues: Bad vs. good adipose tissues

Figures & data

Table 1. Influence of race, aging, reduced physical activity, and physical activity on INTMF in humans

Topic, subjects	Approach	Results	Conclusions	Reference
Aging, 73 y old men and women, over 5 y in the Health, Aging, and Body Composition study cohort (n = 1678).	A single CT 10-mm axial image of the right thigh, CSA muscle and fat, leg muscle strength, and muscle quality	Weight gain did not prevent loss of muscle strength. Age increased INTMF in men and women and, remarkably, INTMF increased with weight loss, weight gain, or with no weight change.	Aging is associated with decreases in muscle strength and quality regardless of body weight changes. The persistence of increases in INTMF indicates a distinct regulation of INTMF.	^79
Physical activity, 6 men and 12 women aged 19–28 y.	A 4-wk control period followed by 4 wk of unilateral lower limb suspension. Multiple axial images with MRI of muscle, SQF, and INTMF, in the thigh and calf.	Reduced physical activity decreased thigh and calf muscle volumes by 7.4–7.9%, associated with increases in INTMF but no change in SQF.	Reduced physical activity in healthy young adults increases INTMF which may contribute to losses in muscle strength.	^80
Aging and physical training, participants represented wide range of ages, mobility levels and co-morbid diseases.	INTMF fat and lean tissue CSA's obtained from bilateral MRI scans of the thigh. 55 and older individuals subjected to a 12 wk resistance training program.	Significant and positive relationship between age and percent thigh INTMF in individuals with a variety of co-morbid conditions. Resistance training decreased INTMF and increased lean tissue.	Resistance training decreases INTMF accretion in older individuals with metabolic and mobility impairments.	^81
Race and obesity, 1105 Caucasian and 518 Afro-Caribbean men aged 65.	Body mass index, total body fat by DEXA, and calf skeletal muscle composition by pQCT	Greater INTMF and lower SQF in Afro-Caribbean men at all levels of total adiposity. Differences in INTMF and SQF fat were independent of age, height, calf skeletal muscle, and total adipose tissue.	INTMF is greater among African than among Caucasian ancestry men despite lower total adiposity. INTMF associated with T2D in both ethnic groups.	^82
Exercise and muscle location, 45 subjects, 56–64 y old, composed of a healthy obese group, a group with diabetes and a group with diabetes and peripheral neuropathy	INTMF fat over the right calf muscle quantified using MRI. Calf muscle divided into two muscles and three compartments. Six minute walk test and physical performance test (PPT) employed.	The gastrocnemius had highest ratio of INTMF /muscle volume. Groups had similar calf muscle or INTMF volumes. Calf INTMF was inversely related to performance on the 6 min walk test and PPT.	Calf INTMF accretion is muscle specific and associated with poor physical performance.	^83
Physical activity in older adults, 70 -89 y old. Eleven men and 31women in a randomized trial, either physical activity (PA; n = 22) or aging health educational control (SA; n = 20) group.	Physical activity intervention included primarily walking and three phases, adoption, transition, and maintenance (week 25 to end). Skeletal muscle and INTMF CSA's calculated from axial CT images of the midthigh level.	Decreased strength adjusted for muscle mass decreased in SA prevented in PA. A significant increase in INTMF was nearly prevented in PA. No change in SQF in either group.	Physical activity can prevent losses of muscle strength and increases in INTMF in older age.	^84

SQF, subcutaneous adipose tissue; INTMF, intermuscular adipose tissue; CT, computed tomography; CSA, cross-sectional area; MRI, magnetic resonance imaging; pQCT, quantitative CT; DEXA, dual-energy X-ray absorptiometry; T2D, type 2 diabetes; PPT, physical performance test; PA, physical activity group; SA, control group.

Table 2. Intramuscular lipid (IML) accretion that occurs naturally is species and muscle dependent

Factor	Species/muscle	Summary
Age	Cattle and pigs, several muscles	Lipid accretion dependent on muscle and species^59,111
	Cattle, LD	Lipid increase between 11 and 15 mo—no change after 15 mo^63
	Cattle	Linear increase in marbling to 200–400 kg—no further increase after 420 kg^112
Gender	Cattle, LD	Marbling lipid highest in heifers, intermediate in steers, and lowest in bulls^113
Diet	Japanese black cattle, LD	Reduced vitamin A serum levels increases marbling^113,114
	Holstein steers, LD	Vitamin A restriction does not influence marbling FCS and FCN^115
	Pigs, LD and BF	Lysine-deficient diet increases lipid^116
	Holstein steers, LD	Marbling FCS influenced by energy level and FCN influenced by energy source^117
	Pigs, BF and LD	Lipid decreased with feed restriction (30–70 kg), not influenced by compensatory growth^118
	Pigs, LD, RF, deep and superficial ST.	Feed restriction reduced lipid in muscle-dependent manner (ST > RF,LD) on a constant age basis^119
	Pigs, LD	Reduced protein and energy diet reduced lipid and FCS, long-term feed restriction reduced lipid and FCN^120
	Yucatan mini-pigs, BF	Overfeeding (4–16 mo) increased FCS and lipid^121
	All meat animals, overall muscularity	Variability of IML may be more efficiently linked when evaluating multiple markers (nutrition, diet frequency, specific metabolites, genetics)^111,122,123
Endocrine	Pigs	Porcine GH decreases overall lipid load^124
	Pigs, trapezius	No influence of IGF-II genotype on FCS and lipid^107
Birth weight	Pigs, LD and ST	Low birth wt increases ST lipid and FCS, but not LD^125
Muscle fiber types	Chickens and glycolytic fibers	Lower lipid content^111
Obesity	Pigs, LD	Increased lipid^126,127

Abbreviations: BF, biceps femoris; LD, longissimus dorsi; ST, semitendinosus; RF, rectus femoris; FCN, fat cell number; FCS, fat cell size.

Table 3. Common genes/genetic markers associated with INTMF and IM fat in humans and animals

Genes/genetic markers	Humans	Animals	References
Adipogenic and lipogenic related	Increased Stearoyl-CoA desaturase SCD1 - SNPs in the 3¢UTR (G > A; C > T)	Increased SCD1 - SNPs in the 3¢UTR (G > A; C > T)—in cattle and pig	^141
		Increased SCD1- LM tissues of Wagyu × Hereford cattle	^142
	PPARγ and coactivator 1α (PGC1α) regulation of pyruvate dehydrogenase (PDK4)	PPARγ, C/EBPα, FABP4, Zfp423—Angus cattle	^97,143
		PPARγ and MAPK signaling—higher expression with IM deposition in Beijing-you chicken	^144
	FLJ20920 through its interaction with PPARγ	Novel porcine FLJ36031 (pFLJ)	^145,146
	Perilipin 2 (PLIN2) facilitates intramyocellular lipid (IMCL) storage	Lipin 1 and Lipin-β - IM deposition in obese pigs	^147,148
Metabolic enzymes	Increased expression of Insulin growth factor-1 (IGF-1) and IGFBP3 with higher body fat	Increased expression of IGF-1 and IGFBP3 with increased muscle growth of cattle	^149,150
Cholesterol and bile acid homeostasis	Lipopolysaccharide (LPS) induces MAPK-dependent proinflammatory cytokine/expression® suppresses PPARγ and insulin responsiveness.	Liver transcriptomics in porcine using RNA seq - differential expression of LPS endotoxin/pro-inflammatory cytokines (LPS/IL-1)	^151,152
Fat mass and obesity-associated (FTO) gene	Homozygous for the risk alleles of SNP rs993939—linked with increased risk for obesity	Mapped between SW1302 and SWR1130 on SSC6 in the porcine adjacent to the region with QTLs for IM percentage	^153,154
Agouti signaling protein (ASIP)	ASIP through interaction with STAT 1/3 (signal transducer and activator of transcription) and PPARγ	ASIP/melanocortin signaling system in chickens	^155,156
		ASIP mRNA >9-fold increase in IM of Japanese Black cattle vs. Holstein	^157

Figure 1. Major metabolic, physiological, and genetic changes associated with different Intermuscular and Intramuscular fat in animals and humans.

Delmonico MJ, Harris TB, Visser M, Park SW, Conroy MB, Velasquez-Mieyer P, Boudreau R, Manini TM, Nevitt M, Newman AB, et al.; Health, Aging, and Body. Longitudinal study of muscle strength, quality, and adipose tissue infiltration. Am J Clin Nutr 2009; 90:1579-85; PMID:19864405; http://dx.doi.org/10.3945/ajcn.2009.28047

 PubMed Web of Science ®Google Scholar

Manini TM, Clark BC, Nalls MA, Goodpaster BH, Ploutz-Snyder LL, Harris TB. Reduced physical activity increases intermuscular adipose tissue in healthy young adults. Am J Clin Nutr 2007; 85:377-84; PMID:17284732

 PubMed Web of Science ®Google Scholar

Marcus RL, Addison O, Kidde JP, Dibble LE, Lastayo PC. Skeletal muscle fat infiltration: impact of age, inactivity, and exercise. J Nutr Health Aging 2010; 14:362-6; PMID:20424803; http://dx.doi.org/10.1007/s12603-010-0081-2

 PubMed Web of Science ®Google Scholar

Miljkovic I, Yerges LM, Li H, Gordon CL, Goodpaster BH, Kuller LH, Nestlerode CS, Bunker CH, Patrick AL, Wheeler VW, et al. Association of the CPT1B gene with skeletal muscle fat infiltration in Afro-Caribbean men. Obesity (Silver Spring) 2009; 17:1396-401; PMID:19553926

 PubMed Web of Science ®Google Scholar

Tuttle LJ, Sinacore DR, Mueller MJ. Intermuscular adipose tissue is muscle specific and associated with poor functional performance. J Aging Res 2012; 2012:172957; PMID:22666591; http://dx.doi.org/10.1155/2012/172957

 PubMedGoogle Scholar

Goodpaster BH, Chomentowski P, Ward BK, Rossi A, Glynn NW, Delmonico MJ, Kritchevsky SB, Pahor M, Newman AB. Effects of physical activity on strength and skeletal muscle fat infiltration in older adults: a randomized controlled trial. J Appl Physiol (1985) 2008; 105:1498-503; PMID:18818386; http://dx.doi.org/10.1152/japplphysiol.90425.2008

 PubMedGoogle Scholar

Cianzio DS, Topel DG, Whitehurst GB, Beitz DC, Self HL. Adipose tissue growth and cellularity: changes in bovine adipocyte size and number. J Anim Sci 1985; 60:970-6; PMID:3988658

 PubMed Web of Science ®Google Scholar

Pethick DW, Harper GS, Oddy VH. Growth, development and nutritional manipulation of marbling in cattle: a review. Aust J Exp Agric 2004; 44:705-15; http://dx.doi.org/10.1071/EA02165

 Google Scholar

Harper GS, Pethick DW. How might marbling begin? Aust J Exp Agric 2004; 44:653-62; http://dx.doi.org/10.1071/EA02114

 Google Scholar

Gorocica-Buenfil MA, Fluharty FL, Reynolds CK, Loerch SC. Effect of dietary vitamin A concentration and roasted soybean inclusion on marbling, adipose cellularity, and fatty acid composition of beef. J Anim Sci 2007; 85:2230-42; PMID:17468427; http://dx.doi.org/10.2527/jas.2006-780

 PubMedGoogle Scholar

Essén-Gustavsson B, Karlsson A, Lundström K, Enfält AC. Intramuscular fat and muscle fibre lipid contents in halothane-gene-free pigs fed high or low protein diets and its relation to meat quality. Meat Sci 1994; 38:269-77; PMID:22059664; http://dx.doi.org/10.1016/0309-1740(94)90116-3

 PubMed Web of Science ®Google Scholar

Schoonmaker JP, Fluharty FL, Loerch SC. Effect of source and amount of energy and rate of growth in the growing phase on adipocyte cellularity and lipogenic enzyme activity in the intramuscular and subcutaneous fat depots of Holstein steers. J Anim Sci 2004; 82:137-48; PMID:14753357

 PubMed Web of Science ®Google Scholar

Heyer A, Lebret B. Compensatory growth response in pigs: effects on growth performance, composition of weight gain at carcass and muscle levels, and meat quality. J Anim Sci 2007; 85:769-78; PMID:17296780; http://dx.doi.org/10.2527/jas.2006-164

 PubMed Web of Science ®Google Scholar

Bee G, Calderini M, Biolley C, Guex G, Herzog W, Lindemann MD. Changes in the histochemical properties and meat quality traits of porcine muscles during the growing-finishing period as affected by feed restriction, slaughter age, or slaughter weight. J Anim Sci 2007; 85:1030-45; PMID:17178814; http://dx.doi.org/10.2527/jas.2006-496

 PubMed Web of Science ®Google Scholar

Gondret F, Lebret B. Feeding intensity and dietary protein level affect adipocyte cellularity and lipogenic capacity of muscle homogenates in growing pigs, without modification of the expression of sterol regulatory element binding protein. J Anim Sci 2002; 80:3184-93; PMID:12542159

 PubMed Web of Science ®Google Scholar

Guillerm-Regost C, Louveau I, Sébert SP, Damon M, Champ MM, Gondret F. Cellular and biochemical features of skeletal muscle in obese Yucatan minipigs. Obesity (Silver Spring) 2006; 14:1700-7; PMID:17062798; http://dx.doi.org/10.1038/oby.2006.195

 PubMedGoogle Scholar

Sørensen MT, Oksbjerg N, Agergaard N, Petersen JS. Tissue deposition rates in relation to muscle fibre and fat cell characteristics in lean female pigs (Sus scrofa) following treatment with porcine growth hormone (pGH). Comp Biochem Physiol A Physiol 1996; 113:91-6; PMID:8624908; http://dx.doi.org/10.1016/0300-9629(95)02038-1

 PubMedGoogle Scholar

Gardan D, Gondret F, Louveau I. Lipid metabolism and secretory function of porcine intramuscular adipocytes compared with subcutaneous and perirenal adipocytes. Am J Physiol Endocrinol Metab 2006; 291:E372-80; PMID:16705057; http://dx.doi.org/10.1152/ajpendo.00482.2005

 PubMed Web of Science ®Google Scholar

Gondret F, Lefaucheur L, Juin H, Louveau I, Lebret B. Low birth weight is associated with enlarged muscle fiber area and impaired meat tenderness of the longissimus muscle in pigs. J Anim Sci 2006; 84:93-103; PMID:16361495

 PubMed Web of Science ®Google Scholar

Hocquette JF, Gondret F, Baéza E, Médale F, Jurie C, Pethick DW. Intramuscular fat content in meat-producing animals: development, genetic and nutritional control, and identification of putative markers. Animal 2010; 4:303-19; PMID:22443885; http://dx.doi.org/10.1017/S1751731109991091

 PubMed Web of Science ®Google Scholar

Jiang Z, Michal JJ, Tobey DJ, Daniels TF, Rule DC, Macneil MD. Significant associations of stearoyl-CoA desaturase (SCD1) gene with fat deposition and composition in skeletal muscle. Int J Biol Sci 2008; 4:345-51; PMID:18825276; http://dx.doi.org/10.7150/ijbs.4.345

 PubMed Web of Science ®Google Scholar

Wang W, Xue W, Jin B, Zhang X, Ma F, Xu X. Candidate gene expression affects intramuscular fat content and fatty acid composition in pigs. J Appl Genet 2013; 54:113-8; PMID:23275256; http://dx.doi.org/10.1007/s13353-012-0131-z

 PubMed Web of Science ®Google Scholar

Cui HX, Liu RR, Zhao GP, Zheng MQ, Chen JL, Wen J. Identification of differentially expressed genes and pathways for intramuscular fat deposition in pectoralis major tissues of fast-and slow-growing chickens. BMC Genomics 2012; 13:213; PMID:22646994; http://dx.doi.org/10.1186/1471-2164-13-213

 PubMed Web of Science ®Google Scholar

Albrecht E, Komolka K, Kuzinski J, Maak S. Agouti revisited: transcript quantification of the ASIP gene in bovine tissues related to protein expression and localization. PLoS One 2012; 7:e35282; PMID:22530003; http://dx.doi.org/10.1371/journal.pone.0035282

 PubMedGoogle Scholar