Table 2.

Functions and predicted targets of miRNAs that are differentially expressed in the same direction in obesity and sarcopenia

MiRNA (family)	Cluster	↑↓	Function in relation to obesity/adiposity/insulin resistance or sarcopenia/muscle/exercise	Sample	Target
Plasma
MiR‐106a‐5p (miR‐17)	MiR‐106a, miR‐18b, miR‐20b, miR‐19b‐2, miR‐92a‐2, miR‐363	↑	Down‐regulated in polycystic ovary syndrome (PCOS) 36 Elevated in aged muscles (mice) and dexamethasone‐treated myotubes; agomir results in down‐regulation of both myogenic regulatory factors (MyoD, MyoG, and MyHC) and phosphorylation of AKT and decreased myotube size 37	Plasma exosomes 36 C2C12 cells 37 Mice 37	PIK3R1 37
MiR‐1224‐5p (miR‐1224)	N/A	↑	Up‐regulated in the liver of obese and high‐fat diet‐fed mice, contributes to hepatic lipid accumulation by targeting AMPKα1 38	Mice 38	AMPKα1 38
MiR‐1246 (miR‐1246)	N/A	↑	Down‐regulated in patients with chronic obstructive pulmonary disease (COPD) and emphysema (n = 20) 39 and amyotrophic lateral sclerosis (ALS) patients (n = 14) 40 Up‐regulated in diabetic nephropathy patients (n = 23); positively correlated with BMI 41	Serum 39 , 41 Plasma 40
MiR‐145‐5p (miR‐145)	MiR‐145, miR‐143	↑	Limited studies on obesity/sarcopenia Up‐regulated in normal‐weight women (n = 11) following a high‐energy/fat breakfast 42	Plasma 42
MiR‐18b‐5p (miR‐17)	MiR‐106a, miR‐18b, miR‐20b, miR‐19b‐2, miR‐92a‐2, miR‐363	↑	Limited studies on obesity/sarcopenia Up‐regulated in PCOS 43 and relapsing multiple sclerosis (MS), may be involved in inflammatory pathways 44 SORBS2 identified as a target in diabetic nephropathy model cells 45 Targets and inhibits IGF‐1, suppressing the activation of p‐AKT, p‐MEK, and p‐ERK1/2 in vitro 46	Serum 43 , 44 HGMCs/HRGECs 45 HRECs 46	SORBS2 45 IGF‐1 46
MiR‐193b‐5p (miR‐193)	MiR‐193b, miR‐365a	↑	Limited studies on obesity/sarcopenia Weak negative correlations with BMI, plasma glucose levels, and insulin response to OGTT in younger adults 47 Targets and decreases expression of FoxO3 in cells, regulating cell cycle and cell proliferation 48	Subcutaneous adipose tissue 47 BRL‐3A 48	FoxO3 48
MiR‐196a‐5p (miR‐196)	N/A	↑	High level of expression in myoblasts, suppresses mitochondrial biogenesis and its master regulator, PGC1β, and ND4. Suppresses osteoclast formation induced by RANKL in Raw264.7 cells 49	C2C12 cells 49 Raw264.7 cells 49
MiR‐197‐3p (miR‐197)	N/A	↑	Increased after high‐intensity resistance exercise in young adults 50 Up‐regulation inhibits GIP and GLP‐1 production through suppression of PCSK1/3 51	Serum 50 STC‐1 cells 51
MiR‐199a‐5p (miR‐199)	MiR‐214	↓	Overexpression of AKT down‐regulates miR‐199a‐5p with a subsequent increase in targets Sirt1 and HiF‐1α in cardiomyocytes 52 Down‐regulated in mild and terminal‐stage ALS 53 and patients with Parkinson's disease 54 Up‐regulated in middle‐aged adults with T2DM; in vitro studies showed that miR‐199a regulates cellular glucose uptake by targeting and suppressing GLUT4 55 Up‐regulated in rat pancreatic β‐cells exposed to high glucose, promotes apoptosis and ROS formation, suppresses SIRT1 56 Inhibition results in decreased myogenic differentiation and increased MyoD1 and Pax7 in human myoblasts. High levels inhibit WNT signalling in HEK293T cells. Overexpression in zebrafish results in disorganization and detachment of myofibres 57	Cardiomyocytes 52 Serum 53 Plasma 55 Induced pluripotent stem cells 54 Rat pancreatic β‐cells 56 Myoblasts, HEK293T cells, zebrafish 57	Sirt1 52 , 56 , 58 HiF‐1α 52 GLUT4 55
MiR‐296‐3p (miR‐296)	MiR‐296, miR‐298	↑	Up‐regulated in PCOS; reduction in miR‐296‐3p promotes cell proliferation 59	Human granulosa cells 59 Human granulosa‐like tumour cells 59	PTEN 59
MiR‐29b‐2‐5p (miR‐29)	MiR‐29b‐2, miR‐29c	↑	Limited studies in the context of muscle/obesity Targets STAT3 in a fibroblast cell line 60	L929 cells 60	STAT3 60
MiR‐301b‐3p (miR‐130)	MiR‐301b, miR‐130	↓	Decreased during myogenic differentiation; may be involved in muscle differentiation by regulating Rb1cc1 61	Chicken myoblasts 61	Rb1cc1 61
MiR‐378c	N/A	↑	Studies not identified in the context of muscle/obesity
MiR‐4732‐5p (miR‐4732)	MiR‐4732, miR‐144, miR‐451a, miR‐451b	↑	Studies not identified in the context of muscle/obesity
MiR‐483‐3p (miR‐483)	N/A	↑	Up‐regulated in hyperglycaemic mice and cardiomyocytes. Overexpression down‐regulates IGF‐1, thus promoting apoptosis in hyperglycaemic cardiomyocytes 62 Overexpression inhibits bovine myoblast cell proliferation through the IGF1/PI3K/AKT pathway; knockdown of miR‐483 enhances the expression of myogenic maker genes MyoD1, MyoG, and MyHC 63 Elevated in Duchenne's muscular dystrophy 64	Mice, H9c2 cell line 62 Bovine myoblasts 63 Serum 64	IGF‐1 62 , 63
MiR‐487a‐3p (miR‐154)	MiR‐1185‐1, miR‐1185‐2, miR‐381, miR‐487a, miR‐487b, miR‐539, miR‐889, miR‐544a, miR‐655, miR‐382, miR‐154, miR‐496, miR‐377, miR‐134, miR‐668, miR‐485, miR‐323b	↓	Studies not identified in the context of muscle/obesity
MiR‐499a (miR‐499) MyomiR	MiR‐499a, miR‐499b Encoded in slow myosin heavy chain genes (Myh7b)—restricted to T1 fibres (expressed in T1 fibres only)	↓	Elevated in patients and carriers (mothers) with Duchenne's muscular dystrophy 65 and COPD (n = 103) and significantly correlated with NF‐κB p50 66 Affected by aerobic exercise—no changes after acute bout in young men 67 ; decreased following acute bout with weight vest with/without nutritional supplementation 68 ; increased in male marathon runners (n = 21) after competitive marathon competition 69 Increased after essential amino acid (EAA) ingestion in young adults (n = 7) 70 Associated with a slow muscle fibre phenotype in human muscle 71 Double knockout miR‐499/miR‐208b mice lost slow Type I myofibres with a concomitant increase in fast Type IIx/d and IIb myosin isoforms; forced expression of miR‐499 converted fast myofibres to slow. Sox6 helps mediate the actions of miR‐499 on slow myofibre gene programming 72 Targets Thrap1 to promote slow muscle fibre type 73 Targets TGF‐βR1, a known regulator of skeletal myoblast development. Knockdown of TGF‐βR1 inhibits myogenic differentiation in C2C12 cells 74 Targets PRDM16, which subsequently promotes myogenic, rather than brown adipogenic, differentiation in mouse skeletal muscle stem cells (SMSCs) 75 Promotes mitochondrial function. Targets Fnip1, a negative regulator of mitochondrial function in myocytes, which leads to activation of PGC‐1α. Fnip1 inhibition stimulates oxygen consumption rates, a sign of mitochondrial function, in myocytes. Mice with muscular dystrophy bred with miR‐499 mice exhibit improved mitochondrial capacity, restored slow‐oxidative muscle fibre programming and greater muscle functionality assessed with treadmill distance 76 Knockdown of p21, a target of miR‐499, decreases mitochondrial fission and cell death in cardiomyocytes exposed to doxorubicin, anti‐tumour drug 77 PTENP1, a target gene of miR‐499, expression is enhanced in diabetic and obese mouse models resulting in impaired AKT/GSK activation and glycogen synthesis contributing to insulin resistance 78 Down‐regulation was observed in diabetic mouse models. Down‐regulation in vitro was shown to impair the insulin signalling, AKT/GSK pathway and glycogen synthesis. PTEN was identified as a target 79	Plasma 65 , 66 , 69 Serum 67 Vastus lateralis 68 , 70 , 71 Mice 71 , 72 , 76 , 77 , 78 , 79 C2C12 cells 72 , 73 , 74 SMSCs 75 H9c2 cells 77 Murine liver cells NCTC1469 78 , 79	Sox6 72 Thrap1 72 , 73 p21 77 TGF‐βR1 74 PRDM16 75 Fnip1 76 PTEN 79 PTENP1 78
MiR‐550a‐3p (miR‐550)	MiR‐550a‐1, miR‐550b‐1	↑	Limited studies in muscle/obesity Down‐regulated in patients with sporadic ALS 80 Associated with parameters of bone formation and microstructure parameters (mineral apposition ratio, bone surface, trabecular bone volume) 81 Down‐regulated in postmenopausal women with fractures older than 6 months; excellent discrimination of patients with low traumatic fractures 82	Peripheral blood 80 Serum 81 , 82
MiR‐576‐5p (miR‐576)	N/A	↑	Studies not identified in the context of muscle/obesity
MiR‐589‐5p (miR‐589)	N/A	↑	Limited studies in muscle/obesity Decreased upon TGF‐β stimulation in control fibroblasts, with no effect seen in COPD fibroblasts 83	Fibroblasts 83
MiR‐766‐3p (miR‐766)	N/A	↑	Decreased in older (60–73 years; n = 51) compared with younger (19–42 years; n = 55) or long‐lived (90–102 years; n = 51) adults. 84 Overexpressed in older adult human dermal fibroblasts (HDFs) 85 Decreased after 12 weeks of endurance training in young men (n = 32) 86 Increased in sedentary T2DM adults (40–70 years; n = 24) who undertook either 4 month resistance or aerobic training 87	PBMCs 84 HDFs 85 HeLa cells 85 Plasma 86 , 87	SIRT6 85
MiR‐92a‐3p (miR‐92a)	MiR‐17, miR‐18a, miR‐19a, miR‐20a, miR‐19b‐1, miR‐92a‐1	↑	Anti‐miR, MRG‐110, was tested in adult men and found to counteract the repression of known miR‐92a‐3p targets, ITGA5 and CD93. Elevated levels of DDIT4, an inhibitor of mTOR, were found in cells treated with MRG‐110 88 In a systematic review, down‐regulated following bariatric surgery 89 Decreased following 20 week aerobic exercise training (n = 20), 90 12 week endurance training in young men (n = 32), 86 and a 6 week cycling training in young men (n = 24) 91 No change following 5 month aerobic training in obese older adults (n = 33); however changes in miR‐92a positively correlated with changes in gait speed following intervention 92 MiR‐92a targets SMAD7, inhibition of miR‐92a led to increased mitochondrial content and oxygen consumption of brown adipocytes; inhibition of miR‐92a led to promotion of SMAD7 and subsequent suppression of p‐SMAD3/SMAD3. Inhibition of miR‐92a promoted differentiation of brown adipocytes. 93 Negatively correlated with BAT activity in young adults (n = 41); down‐regulated in the serum exosomes of mice with active BAT 94 Gradually up‐regulated with age (22, 40, 59, and 70 years) in men and women 95	Whole blood 88 CD4+ T cells 88 Plasma 86 , 89 , 92 Serum 90 , 94 , 95 C2C12 cells 93 Vastus lateralis 91 Mice 94	ITGA5 88 CD93 88 SMAD7 93
Serum
MiR‐23a‐3p (miR‐23)	Mir‐23a, miR‐27a, miR‐24‐2	↑	Significantly down‐regulated in SAT and VAT of obese participants and significantly correlated with measures of adiposity (BMI, waist circumference, insulin measures). Involved in the regulation of PTEN, although the molecular mechanism is unclear 96 In young men (n = 7), increased following resistance or endurance exercise and protein ingestion 97 Increased following EAA ingestion alone 70 Decreased after an acute bout of endurance exercise in young adults (n = 9) 98 Up‐regulated in ALS. Targets PGC‐1α with subsequent effects on mitochondrial biogenesis and activity 99 Protects muscles from atrophy by targeting atrogin‐1/MAFbx1 and MURF‐1. Overexpression counteracts muscle atrophy induced by dexamethasone in myotubes and glucocorticoids in mice 100	VAT, SAT 96 Vastus lateralis 70 , 98 , 99 Mice 99 , 100 Adipocytes 96 C2C12 cells 100	Atrogin‐1/MAFbx1 100 MURF‐1 100 PGC‐1α 99 , 101
Vastus lateralis
MiR‐424‐5p (miR‐322)	MiR‐424, miR‐503, miR‐542, miR‐450a‐2, miR‐450a‐1, miR‐450b	↑	Down‐regulated in young women with PCOS (n = 24). 43 No difference between obese (n = 21) and NW (n = 19) women but correlated with waist circumference 102 Increased in cachectic cancer patients 103 Up‐regulated in muscle wasting conditions—ICU‐acquired weakness and COPD. Overexpression causes a reduction in muscle diameter of mice 33 Saturated fat/high‐fat diet impairs insulin signalling (INSR and IRS‐1) and up‐regulated miR‐424‐5p in hepatocytes and mice. Overexpression causes a significant decrease in insulin‐induced glycogen synthesis in hepatocytes. INSR is a direct target 104 Targets IGF‐1 in mice and human myocytes 105	Serum 43 Mice 33 , 104 Vastus lateralis 33 , 103 SAT 102 Plasma 102 Hepatocytes 104 C2C12 cells 105 Human myoblasts 105	SMAD7 33 INSR 104 IGF‐1 105

↑, up‐regulated in sarcopenia/obesity; ↓, down‐regulated in sarcopenia/obesity; HGMCs, human glomerular mesangial cells; HRECs, human retinal endothelial cells; HRGECs, human renal glomerular endothelial cells; PBMCs, peripheral blood mononuclear cells.