Experimental Gerontology 179 (2023) 112250

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Experimental Gerontology
journal homepage: www.elsevier.com/locate/expgero

Effects of Yijinjing combined with resistance training on body fat

distribution and hepatic lipids in middle-aged and older people with
prediabetes mellitus: A randomized controlled trial
Yanwei Cai a, c, Suijun Wang b, Shasha Wang a, Qing Gu b, Yunda Huang a, Jingyuan Li a,
Ru Wang a, *, Xiangyun Liu a, *
a
Shanghai University of Sport, Shanghai 200438, China
b
Department of Endocrinology, Shidong Hospital, Yangpu District, Shanghai 200433, China
c
Shanghai Deji Hospital, Qingdao University, Putuo District, Shanghai 200331, China

A R T I C L E I N F O A B S T R A C T

Section Editor: Jiankang Liu Purpose: This randomized controlled trial aimed to study the effects of Yijinjing plus Elastic Band Resistance
exercise on intrahepatic lipid (IHL), body fat distribution, glucolipid metabolism and biomarkers of inflammation
Keywords: in middle-aged and older people with pre-diabetes mellitus (PDM).
Physical activity Participants agesnd methods: 34 PDM participants (mean age, 62.62 ± 4.71 years; body mass index [BMI], 25.98
Liver fat
± 2.44 kg/m2) were randomly assigned to the exercise group (n = 17) or control group (n = 17). The exercise
Obesity
group performed moderate-intensity Yijinjing and Elastic Band Resistance training 5 times per week for 6
Pre-diabetes
Geriatrics months. The control group maintained their previous lifestyle. We measured body composition (body weight and
body fat distribution), IHL, plasma glucose, lipid and the homeostatic model assessment of insulin resistance
(HOMA-IR), inflammatory cytokines at baseline and 6 months.
Results: Compared with baseline, exercise significantly reduced IHL (reduction of 1.91 % ± 2.61 % vs an increase
of 0.38 % ± 1.85 % for controls; P = 0.007), BMI (reduction of 1.38 ± 0.88 kg/m2 vs an increase of 0.24 ± 1.02
kg/m2 for controls; P = 0.001), upper limb fat mass, thigh fat mass and whole body fat mass. Fasting glucose,
HOMA-IR, plasma total cholesterol (TC), and triglyceride (TG) were decreased in the exercise group (P < 0.05).
There were no effects of exercise on liver enzyme levels and inflammatory cytokines. The decrease in IHL was
positively correlated with the decreases in BMI, body fat mass and HOMA-IR.
Conclusion: Six months of Yijinjing and resistance exercise significantly reduced hepatic lipids and body fat mass
in middle-aged and older people with PDM. These effects were accompanied by weight loss, improved glycolipid
metabolism and insulin resistance.

1. Introduction
Aging is an inherent and complicated process that leads to the
development of Pre-diabetes Mellitus (PDM) and other metabolic dis­
eases. PDM is a condition in which plasma glucose level is higher than
the normal range but does not meet the diagnostic criteria for clinical
diabetes (Wang et al., 2019). It is a subclinical state of impaired fasting
glucose, impaired glucose tolerance, or both (Braga et al., 2018). The
World Health Organization (WHO) defines PDM as fasting blood glucose
(FBG) of 6.1–7.0 mmol/L, 2 h postprandial blood glucose (2hPBG) of
7.8–11.1 mmol/L, and glycosylated hemoglobin (HbAlc) of 6.0 %–6.4 %
(Punthakee et al., 2018). Obesity and liver fat accumulation are high-
risk factors (Ligthart et al., 2016). Exercise training is an effective
non-pharmacological tool for the management of PDM. The American
College of Sports Medicine (ACSM) physical activity guidelines recom­
mend that adults with glucose metabolism disorders should do 150 min
or more of physical activity per week because it can lower blood glucose
(Stefani and Galanti, 2017). It also recommends resistance exercise for
health benefits in patients without contraindications, and the combi­
nation of aerobic and resistance training may be the most effective ex­
ercise modality for controlling glucose and lipids in type 2 diabetes
(T2DM) (Kirwan et al., 2017). Unfortunately, most middle-aged and

* Corresponding authors.
E-mail addresses: wangru0612@163.com (R. Wang), liuxy_666666@126.com (X. Liu).

https://doi.org/10.1016/j.exger.2023.112250
Received 11 April 2023; Received in revised form 1 June 2023; Accepted 26 June 2023
Available online 29 June 2023
0531-5565/© 2023 Published by Elsevier Inc. This is an open access article under the CC BY-NC-ND license (http://creativecommons.org/licenses/by-nc-nd/4.0/).
Y. Cai et al.
older people with PDM do not adhere to these exercise recommenda­
tions due to poorer cardiopulmonary function and joint pain (Bowden
Davies et al., 2019).
Lack of physical activity may be particularly harmful in elderly with
PDM given the coexisting sarcopenia or osteoporosis. Inactivity com­
bined with obesity aggravates the anabolic resistance to aging and ac­
celerates the progression of insulin resistance and systemic hypo-
inflammation (Bowden Davies et al., 2019). Studies have observed an
increase in fat mass and a decrease in muscle mass in older adults
(Chung et al., 2013) and the accumulation of intrahepatic lipid (IHL) is
associated with impaired beta-cell function (Finucane et al., 2014). A
study found that obese patients with T2DM have increased fat accu­
mulation in the liver and IHL content that correlates with insulin
resistance (IR), dyslipidemia and inflammatory markers (Kelley et al.,
2003). Liver fat is an important source of free fatty acid (FFA) because of
its high lipolysis rate (Boden, 2009), and FFA can aggravate IR and
inhibit glucose uptake and utilization (Boden, 2008). In addition, FFA
also downregulates the level of silence information regulator 1 (SIRT1)
(Long et al., 2019), which inhibits the transcription and activation of
nuclear factor kappa B (NF-κB) in liver adipose tissues (Schug and Li,
2011). NF-κB activation increases the transcription of proinflammatory
cytokines, including interleukin-6 (IL-6) and tumor necrosis factor α
(TNF- α) (Tacke et al., 2009). These inflammatory and metabolic regu­
lators can induce low-grade inflammation and affect blood glucose
metabolism.
Traditional Chinese sports are performed slowly and gently, suitable
for the middle-aged and elderly people (Guo et al., 2016). However, the
benefits of these sports have not been adequately documented and
studied. Currently, most studies have explored the effects of tai chi on
diabetes but have not evaluated other types of traditional exercises, and
these studies still have the following limitations: (1) The intervention
time is short, and the long-term intervention effect needs to be moni­
tored; (2) the main index of weight loss effect is bodyweight, which does
not describe regional changes in body fat distribution and composition;
(3) it does not pay attention to the visceral fat; and (4) trials are needed
to investigate the complex interactions between exercise and inflam­
matory markers. Previous studies by our group have found that Yijinjing
can reduce body weight and improve glucolipid metabolism in old pa­
tients with benign prostatic hyperplasia (Liu et al., 2020). Yijinjing is a
traditional Chinese exercise that benefits the bones, muscles and flexi­
bility of older people (Li et al., 2020). Studies have shown that regular,
long-term practice of Yijinjing can lower blood sugar and lipids, and
prevent cardiovascular disease. (Kong and Shi, 2019)According to Chi­
nese medicine, the specific form of Yijinjing exercises can work on liver
fascia, improving liver and kidney function. And resistance exercise
increases lipocalin, reduces FFA and prevents fat accumulation. It has
been suggested that combined aerobic and resistance training has shown
additional benefits in improving HbAlc and increasing insulin sensitivity
(Cuff et al., 2003; Balducci et al., 2004). So, we conducted a randomized
controlled trial to study the effect of six months of Yijinjing combined
with resistance exercise on glucolipid metabolism, body fat distribution
and IHL in middle-aged and older people with PDM, and preliminarily
explore the potential molecular mechanisms underlying these effects.
2. Material and methods
2.1. Participants
The study is a randomized controlled trial approved by Shanghai
University of Sport Scientific Research Council (Clinical Trials
ChiCTR2100054684). We registered the basic information of the par­
ticipants who finally met the inclusion criteria, had established health
records, and signed the informed consent form. The sample size was
calculated based on change in IHL from previous research. Twelve
weeks of aerobic exercise resulted in a 10.3 % relative reduction in IHL,
and resistance training resulted in a 12.6 % relative reduction in IHL
2
Experimental Gerontology 179 (2023) 112250
(Charatcharoenwitthaya et al., 2021). According to these reported re­
sults, we expected the exercise group to have a 15 % relative reduction
in IHL after the six-month training program, and the standard deviation
is 11.7 %, α = 0.05, and power = 0.80. We needed a minimum sample
size of 11 participants in each group. At an attrition rate of 20 %, a total
sample size of 28 participants was required. The inclusion and exclusion
criteria were as follows: 1) FBG of ≥6.1 or <7 mmol/L or 2hPBG of ≥7.8
or <11.1 mmol/L. 2) Age between 50 and 70, the exercise fewer than
two times a week. 3) Overweight or obesity: central obesity (male waist
circumference ≥ 85 cm, and female waist circumference ≥ 80 cm).
Subjects were excluded when they had medical conditions preventing
participation in the exercise program, or had contraindications to
magnetic resonance imaging (MRI). A total of 34 subjects were
randomly included and divided into two groups with 17 people in each
group by using computer-generated numbers. The flowchart of trial
participants is shown in Fig. 1. Participants in the control group main­
tained their previous diet, medication and lifestyle, whereas those in the
exercise group received progressive intensity Yijinjing combined with
resistance training. All participants were followed up on a regular basis
to assess current lifestyle and health-related issues.
2.2. Exercise intervention
2.2.1. Type
Yijinjing: Yijinjing is Li Wei’s version, which is promoted by the
General Administration of Sports of China, with a total of about 13 min
of movements. The 12 movements included Wei Tuo Presenting the
Pestle (three movements), Plucking a Star and Exchanging a Star Clus­
ter, Three Plates Falling on the Floor, Displaying Paw-Style Palms like a
White Crane Spreading Its Wings, Pulling Nine Cows by Their Tails, Nine
Ghosts Drawing Swords, Black Dragon Displaying Its Claws, Tiger
Springing on Its Prey, Bowing Down in Salutation, and Swinging the
Tail. The whole set of Yijinjing movements consisted of stretches and
gentle movements, with the emphasis on stretching the muscles and
bones, accompanied by breathing exercises to make the body and mind
pleasant.
Resistance exercise: We used elastic bands for the exercises,
including five movements. The exercise involved the shoulder muscles,
which play a major role in daily life, and deltoid and biceps, and semi-
squat and squat were performed to exercise legs and buttocks. The full
set of movements took approximately 8 min. All elastic belts were
purchased from Li-Ning (China) Sports Goods Co., Ltd. Men used elastic
belts with a load of 35 pounds (1500 mm × 1500 mm × 0.5 mm), and
women used elastic belts with a load of 25 pounds (1500 mm × 150 mm
× 0.4 mm).
2.2.2. Frequency and time
The exercises were conducted in a park close to the subjects’ homes.
All subjects were scheduled for exercise training five times per week for
over six months. The exercise consisted of four phases: warm-up,
Yijinjing, resistance exercise, and cool down. In the first two months,
they performed Yijinjing twice a day and two sets of resistance exercises,
and each session lasted for approximately 47 min. In the third and fourth
months, they performed Yijinjing three times a day and three sets of
resistance exercises, and each session lasted for approximately 68 min.
In the fifth and sixth months, three times of Yijinjing and four sets of
resistance movements were carried out every day, and each class lasted
for approximately 76 min.
2.2.3. Intensity and volume
We used moderate intensity exercise, and the patient felt warm and
slightly sweaty. Heart rate maximum (HRmax) = 207–0.7 × age, Resting
heart rate (HRrest) is measured with a heart rate monitor at the first
medical examination, and the expected exercise intensity was 60 %–70
%. Target heart rate (THR) = (HRmax – HRrest) × Intensity + HRrest.
Rating of Perceived Exertion was used as an auxiliary criterion, and the
Y. Cai et al.
Fig. 1. Flowchart of trial participants.
values should be between 9 and 11. The exercise sessions were super­
vised by accredited exercise specialists, and adherence was ensured by
documenting the sessions.
2.3. Measurement of parameters
2.3.1. Anthropometry and biochemical measurements
Before the study, participants underwent a comprehensive medical
history, physical examination, and investigation of diet he and exercise
habits to screen for any metabolic disorders. After overnight fasting
(>10 h), anterior cubital venous blood was taken for the measurement of
biochemical data. FBG, 2hPBG, fasting insulin (FINS), total cholesterol
(TC), triglyceride (TG), low-density lipoprotein (LDL-C), high-density
lipoprotein (HDL–C), FFA, HbA1c, alanine aminotransferase (ALT),
aspartate aminotransferase (AST), and alkaline phosphatase (ALP) were
measured using an automatic biochemical analyzer. Hepatic inflam­
matory factors NF-κBp65, IL-6, and TNF-α and anti-inflammatory factors
SIRT1 were detected with ELISA. We used FBG × FINS/22.5 to calculate
HOMA-IR.
2.3.2. IHL measured by magnetic resonance imaging
IHL was measured with a 3.0T magnetic resonance scanner
(Siemens, Shanghai. China). All subjects were strictly fasted for >4 h
before the examination to avoid the movement artifacts caused by
gastrointestinal peristalsis. Abdominal breathing and breath holding
training were performed before the examination until the subjects can
hold their breath for >15 s. The scanning area covered the entire liver.
Dixon–Vibe sequence images were collected by professional magnetic
resonance operators, and the scanning parameters were as follows:
repetition time, 8.9 ms; echo time, 1.2 ms; slice thickness, 5 mm; flip
angle, 4◦ ; and FoV read, 380 mm. Through the inverse phase image of
the liver obtained during scanning, the axial fat content image of the
liver expressed in gray scale was obtained. The fat fraction map was
transmitted to a Siemens post-processing workstation, and the region of
interest (ROI) is selected by using the signal measurement tool. The
region of interest is to avoid large blood vessels and bile ducts as far as
possible, and the fat content in four regions is selected, ROI area is be­
tween 3 and 4 cm2 (Campo et al., 2017), the IHL in ROI was obtained
3
Experimental Gerontology 179 (2023) 112250
directly, and its average value was used as the Proton Density Fat
Fraction (MRI–PDFF value). According to the results of Tang et al. (Tang
et al., 2013), the best cutoff values of MRI–PDFF for distinguishing the
steatosis of the liver are 6.4 %, 17.4 %, and 22.1 %.
2.3.3. Body fat distribution measured by DEXA
The fat content of the upper limbs, thighs, torso, android area,
gynoid area, and whole body were measured with Dual Energy X-ray
Absorptiometry (DEXA) using lunar prodigy (software version 12.2, GE-
Health care, Shanghai, China). The scanner performs standardized
calibration before each test. The region of the torso of the subjects was
automatically determined as upper limbs, lower limbs, torso, waist and
abdomen, and abdomen and buttocks in the DEXA scanner. The scanner
can accurately measure the fat mass of each part.
2.4. Statistical analysis
SPSS software package version 24.0 was used in analyzing data.
Categorical variables (gender) were expressed in frequencies and per­
centages. The normality of measurement data was evaluated with Sha­
piro Wilks test. Data conforming to a normal distribution and
homogeneity of variance were represented as mean ± standard devia­
tion (− X ± SD), and data with non-normal distribution were represented
with median and quartile (M [P25, p75]). Intention to treat (ITT) was
used for analysis of trials with missing outcome data. Between-group
differences were evaluated using an un-paired t-test, and within-group
differences were evaluated using a paired t-test. Relationships be­
tween change in IHL with intervention and change in other metabolic
variables during treatment were determined with Pearson correlation
coefficients when the data conformed to a normal distribution. For data
with non-normal distribution, Spearman correlation analysis was used.
Statistical significance was set at a P value of <0.05.
3. Results
3.1. Patient characteristics
Three exercise group members withdrew during the experiment due
Y. Cai et al. Experimental Gerontology 179 (2023) 112250

to family troubles and low back pain. The average age of the participants Table 2
was 62.62 ± 4.71 years, and 38.2 % of the participants were males. The Changes observed after six months in the exercise and control groups.
average weight was 70.01 ± 10.27 kg, and the average BMI was 25.98 Exercise (n = 17) Control (n = 17)
± 2.45 kg/m2. The two groups were well matched for age, weight, and
Baseline Post- Baseline Post-
BMI (Table 1). treatment treatment

70.70 ± 66.72 ± 69.31 ± 68.87 ±

Body weight, kg
9.57 10.20* 11.17 11.48
3.2. Exercise reduces body fat mass 26.11 ± 24.75 ± 25.84 ±
BMI, kg/m2 26.09 ± 2.84
2.24 2.36* 2.70
As shown in Table 2, after six months of exercise, the average values Upper limb fat
2.38 ± 0.81 2.25 ± 0.73* 2.42 ± 0.55 2.47 ± 0.56
of body weight, BMI, the fat mass of upper limbs, thighs, android and mass, kg
Thigh fat mass,
gynoid area of the exercise group decreased by 5.21 %, 5.46 %, 9.61 %, 5.41 ± 1.08 4.89 ± 0.87* 6.10 ± 1.37 6.16 ± 1.60
kg
11.62 %, 2.04 %, and 5.20 % respectively. In the control group, the Android fat
2.45 ± 0.63 2.40 ± 0.59* 2.37 ± 0.48 2.34 ± 0.53
average values of body weight and fat mass in the android and gynoid mass, kg
area decreased by 0.63 %, 1.27 %, and 2.76 % respectively, whereas Gynoid fat
3.27 ± 0.63 3.10 ± 0.46* 3.62 ± 0.67 3.52 ± 0.62
mass, kg
BMI, upper limb and thigh fat mass increased by 0.97 %, 2.07 %, and
Trunk fat mass, 13.76 ± 13.48 ±
0.98 % respectively. Although no significant difference in body fat kg 3.15
13.59 ± 3.05
2.65
13.14 ± 2.65
percentage was found between the two groups, the difference in body fat Body fat mass, 22.36 ± 21.54 ± 22.81 ±
22.48 ± 4.17
percentage change was significant between the groups (− 1.45 ± 2.27 kg 4.60 3.96* 4.29
vs. 0.27 ± 1.21 %; P = 0.013; Table 3). Body fat
36.6 35.6 36.4 37.8
percentage,
(27.6,40.5) (28.7,38.7) (32.2,40.3) (33.3,40.9)
%
IHL, % 8.45 ± 4.65 6.85 ± 4.89* 6.81 ± 4.90 7.19 ± 4.75
3.3. Exercise reduces IHL 0.60 (0.55, 0.61 (0.43, 0.52(0.41, 0.62(0.47,
FFA, mmol/L
0.65) 0.75) 0.72) 0.78)
The results of MRI showed a substantial decrease in IHL in the ex­ FBG, mmol/L 6.26 ± 0.53 5.99 ± 0.54* 6.04 ± 0.54 6.08 ± 0.60
2hPBG, mmol/
ercise group relative to 6 months before (8.45 ± 4.65 % vs. 6.85 ± 4.89 9.11 ± 2.03 9.24 ± 3.18 9.26 ± 1.39 9.52 ± 2.19
L
%; P = 0.013; Table 2). The IHL of the control group was higher than HOMA-IR 3.07 ± 1.45 2.63 ± 1.30* 2.91 ± 1.13 2.49 ± 1.17
that before intervention (6.81 % ± 4.90 % vs. 7.19 % ± 4.75 %; P = HbA1c, % 5.98 ± 0.55 6.03 ± 0.31 5.68 ± 0.35 5.84 ± 0.37
0.406; Table 2). Difference in IHL change between the two groups was TC, mmol/L 5.82 ± 1.02 5.32 ± 1.30* 5.49 ± 1.03 5.19 ± 0.68*
statistically significant (− 1.91 ± 2.61 % vs. 0.38 % ± 1.85 %; P = 0.007; 1.50 (1.03, 1.34 (0.86, 1.16 1.03 (0.81,
TG, mmol/L
2.25) 1.74)* (0.91,1.53) 1.61)
Table 3). The above results show that after six months of exercise, the
LDL-C 3.69 ± 0.68 3.76 ± 1.04 3.50 ± 0.71 3.34 ± 0.64
IHL of the exercise group decreased by 18.9 %, while that of the control 1.42 (1.25, 1.30 (1.13, 1.49 (1.23, 1.40 (1.19,
HDL-C
group increased by 5.58 %. Although there was no significant difference 1.66) 1.53)* 1.73) 1.53)*
in IHL between the two groups at the end of the six-month intervention, AST, U/L
22.0 (20.5, 21.0 (19.0, 25.0 (19.5, 25.0 (20.5,
25.5) 27.0) 31.0) 30.0)
three people in the exercise group transferred from clinically meaningful
23.0 (17.0, 20.0 (18.0, 22.0 (16.5, 20.0 (16.5,
nonalcoholic fatty liver disease (NAFLD) to normal range (<6.4 % IHL), ALT, U/L
30.5) 25.0) 29.5) 31.5)
and 1 person changed from grade 2 NAFLD to grade 1 NAFLD (<17.4 % 70.41 ± 70.27 ± 93.35 ± 85.82 ±
ALP, U/L
IHL). The liver fat fraction of the same patient before and after inter­ 20.89 18.98 24.02 27.16
vention is shown in Fig. 2. 15.00 ± 15.51 ±
SIRT1, ng/mL 13.69 ± 3.35 14.46 ± 2.95
2.04 3.10
NF-κBp65,
4.72 ± 0.72 4.23 ± 0.68 4.07 ± 0.75 4.23 ± 0.81
μmol/L
3.4. Exercise reduces fasting blood glucose and insulin resistance 29.90 ± 36.26 ± 34.48 ± 41.62 ±
IL-6, pg/mL
8.20 18.55 11.25 11.43
The effects of six-month intervention on the metabolic indexes of the TNF-α, pg/mL
51.31 ± 54.42 ± 58.81 ± 60.67 ±
18.21 18.68 19.84 20.20
two groups varied (Table 2). The FBG (P = 0.021), HOMA-IR (P =
0.022), TC (P = 0.012), TG (P = 0.033), and HDL-C (P = 0.001) of the Data conforming to a normal distribution and homogeneity of variance were
exercise group decreased substantially after six months of intervention, represented as mean ± standard deviation (− X ± SD), and data with non-normal
whereas the HDL-C (P = 0.013), TC (P = 0.039) of the control group distribution were represented with median and quartile (M [P25, P75]).
decreased substantially after six months, and other metabolic indexes Abbreviation: ALP = Alkaline phosphatase; ALT = Alanine aminotransferase;
did not change substantially. In the exercise group, FBG returned to AST = Aspartate aminotransferase; FBG = fasting blood glucose; FFA = free fatty
acids; HDL-C = high-density lipoprotein cholesterol; HOMA-IR = homeostasis
normal in 4 participants (<6.1 mmol/L), 2hPBG decreased to normal in
model assessment of insulin resistance; IHL = intrahepatic lipid; LDL-C = low-
3 participants (<7.8 mmol/L).
density lipoprotein cholesterol; TC = total cholesterol; TG = triglyceride; 2hPBG
= 2-h postprandial blood glucose.
Table 1 *
Significant difference baseline versus post-treatment (P < 0.05).
Baseline characteristics of the study participants.
Exercise (n = 17) Control (n = 17) P value 3.5. Exercise fails to reduce inflammatory cytokines
Age, year 63.41 ± 5.06 61.82 ± 4.33 0.333
Men/women, n/n 8/9 5/12 – No significant changes in the levels of SIRT1, IL-6, and TNF- α were
Body weight, kg 70.70 ± 9.57 69.31 ± 11.17 0.700 found between the two groups (Table 2). No significant changes in the
BMI, kg/m2 26.1 ± 2.2 25.8 ± 2.7 0.755
levels of SIRT1, NF-κBp65, IL-6, and TNF- α were found between the two
DBP 144.3 ± 19.2 134.7 ± 15.7 0.118
HR 74.7 ± 8.4 76.4 ± 12.0 0.623 groups. The SIRT1 levels of both groups decreased (− 1.21 ± 4.33 vs.
SBP 85.2 ± 12.0 80.4 ± 8.6 0.192 − 1.05 ± 4.30 ng/mL; P = 0.913; Table 3), the IL-6 of both groups
WHR 0.89 ± 0.05 0.88 ± 0.04 0.640 increased (6.38 ± 17.90 vs. 7.14 ± 17.04 pg/mL; P = 0.903; Table 3),
Data are presented as mean ± SD. and the TNF- α showed an increasing trend (3.22 ± 22.34 vs. 1.87 ±
Abbreviation: BMI = body mass index; DBP = diastolic blood pressure; HR = 22.23 pg/mL; P = 0.866; Table 3). NF-κBp65 decreased in the exercise
heart rate; SBP = systolic blood pressure; WHR = waist hip rate. group and increased in the control group (− 0.48 ± 0.79 vs. 0.15 ± 1.29

4
Y. Cai et al. Experimental Gerontology 179 (2023) 112250

Table 3 liver fat, (2) a 5.63 % reduction in body weight, (3) a 14.33 % reduction
Changes with exercise training. in HOMA-IR, and (4) a 4.31 % reduction in FBG. In addition, the fat mass
ΔExercise (n = 17) ΔControl (n = 17) P value in the upper limbs, thighs, android area, and gynoid area was also
2 significantly reduced, accompanied by a decrease in TC and TG. More­
BMI, kg/m − 1.38 ± 0.88 0.24 ± 1.02 0.001**
Upper limb fat mass, kg − 0.22 ± 0.24 0.05 ± 0.37 0.019* over, a decrease in IHL was positively correlated with weight loss, a
Thigh fat mass, kg − 0.67 ± 0.48 0.17 ± 0.76 0.001** decrease in body fat mass and improvement in IR. However, 6 months of
Android fat mass, kg − 0.15 ± 0.23 0.02 ± 0.35 0.133 exercise had no significant effect on circulating markers of inflammation
Gynoid fat mass, kg − 0.23 ± 0.34 − 0.06 ± 0.24 0.112 and liver enzyme levels.
Trunk fat mass, kg − 0.67 ± 1.49 − 0.10 ± 1.27 0.260
Body fat mass, kg − 1.58 ± 2.03 0.09 ± 1.13 0.008**
Weight loss in older adults is controversial due to aging, decreased
Body fat percentage, % − 1.45 ± 2.27 0.27 ± 1.21 0.013* exercise capacity, and the potential loss of muscle and bone (Waters
IHL,% − 1.91 ± 2.61 0.38 ± 1.85 0.007** et al., 2013). Although regular exercise can improve physical function
FFA, mmol/L − 0.01 ± 0.16 0.04 ± 0.18 0.408 and reduce IHL (Perseghin et al., 2007), the most appropriate form of
FBG, mmol/L − 0.27 ± 0.40 0.04 ± 0.41 0.039*
exercise for older adults has not been studied. Ross et al. (Ross et al.,
2hPBG, mmol/L − 0.35 ± 2.41 0.26 ± 1.81 0.420
HOMA-IR − 0.64 ± 0.96 − 0.43 ± 1.10 0.568 2000) showed that no weight loss exercise can reduce abdominal fat and
HbA1c, % − 0.35 ± 2.41 0.26 ± 1.81 0.420 visceral fat, this indicates that exercise can directly reduce IHL without
SIRT1, ng/mL − 1.21 ± 4.33 − 1.05 ± 4.30 0.913 losing weight (Keating et al., 2015; Johnson et al., 2009). But in our
NF-κBp65, μmol/L − 0.48 ± 0.79 0.15 ± 1.29 0.106 study, the older adults in the exercise group showed 5.22 % body weight
IL-6, pg/mL 6.38 ± 17.90 7.14 ± 17.04 0.903
TNF-α, pg/mL 3.22 ± 22.34 1.87 ± 22.23 0.866
loss, which was positively correlated with IHL reduction. Our study
confirmed that exercise-induced moderate weight loss had a significant
Data are presented as mean ± SD. effect on IHL, and IHL reduction was related to improvement in the IR.
Abbreviation: BMI = body mass index; IHL = intrahepatic lipid; FFA = free fatty
acids; FBG = fasting blood glucose; 2hPBG = 2-h postprandial blood glucose;
HOMA-IR = homeostasis model assessment of insulin resistance.
* Table 4
P < 0.05.
** Correlations of the indicated parameters withΔIHL content in the whole study
P < 0.01.
population.
R P
pg/mL; P = 0.106; Table 3).
ΔBMI 0.468 0.007**
ΔAndroid fat mass 0.294 0.109
3.6. Relationship between change in IHL and other variables ΔGynoid fat mass 0.270 0.142
ΔBody fat mass 0.356 0.049*
We analyzed the factors that were associated with the change in IHL. ΔFFA 0.117 0.524
0.569 0.001**
The results showed significant moderate positive correlation between ΔHOMA-IR
ΔTC 0.306 0.088
ΔIHL and ΔBMI (P = 0.007); ΔHOMA-IR (P = 0.001). A weak positive ΔTG 0.054 0.768
correlation exists between ΔIHL and Δbody fat mass (P = 0.049). No ΔNF-κB p65 0.210 0.248
significant correlation was found in others (Table 4). ΔSIRT1 0.023 0.903
ΔIL-6 0.170 0.351
ΔTNF-α 0.129 0.482
4. Discussion
Abbreviation: BMI = body mass index; FFA = free fatty acids; HOMA-IR = ho­
This trail examined the effects of Yijinjing combined with resistance meostasis model assessment of insulin resistance; IHL = intrahepatic lipid; TC =
total cholesterol; TG = triglyceride.
exercise in reducing ectopic liver fat and fat mass in different parts of the *
P < 0.05.
body in middle-aged and elderly people with PDM. The data show that 6 **
P < 0.01.
months of exercise resulted in the following: (1) a 18.93 % reduction in

Fig. 2. Female, 64 years old, MRI-PDFF images at the 1st and 6th month. (A) Grayscale diagrams of liver fat content in the first month. (B) Grayscale diagrams of
liver fat content in the sixth month. The circles in the pictures are the ROIs of different locations selected, and the ratio of fat content can be directly obtained (the
value 1 in the figure represents 0.1 % of intrahepatic fat content). The subject’s IHL decreased substantially.

5
Y. Cai et al.
This indicates that the risk reduction of T2DM is usually associated with
moderate weight loss, and this reduction effect may be achieved by
reducing liver fat. We used dual-energy X-rays to accurately measure
changes in body weight and fat mass at various parts of the body in the
middle-aged and elderly people in this study. We found that Yijinjing
combined with resistance exercise can effectively reduce the fat mass of
upper limbs, thighs, waist and abdomen, but has no significant effect on
trunk fat mass. This may be related to the upper limbs constantly
swinging and supporting the body and the lower limbs needing to sup­
port the body standing for a long time for static contraction. However,
the trunk thoracic and back muscles were not fully mobilized, so there
was no significant change in trunk fat mass. The difference in the degree
of fat mass reduction in different areas may be related to the structural
characteristics of adipose tissue in different areas: aerobic exercise re­
distributes blood in the body, abdominal fat and visceral fat are more
easily mobilized and oxidation is more active. We used HOMA-IR to
diagnose insulin resistance and selected 2.78, 3.01, and 3.56 as the
cutoff point to judge the occurrence of IR. The data were obtained from a
study on the elderly in Shanghai, China (Li et al., 2019).
IHL may cause dysglycemia and dyslipidemia because of its high
metabolic activity, which increases FFA in the circulatory system
(Wiklund et al., 2008). The inflammation hypothesis suggests that
excessive FFA can reduce the level of SIRT1 and activate the NF-κB
signal pathway, thus increasing the levels of proinflammatory factors,
including TNF-α and IL-6, and leading to IR and chronic low-grade
inflammation (Boden, 2011). A study using nicotinic to reduce plasma
FFA found a decrease in IHL and an increase in markers of IR (Hu et al.,
2012). Bluher et al. (Blüher et al., 2005) found that increased insulin
sensitivity was significantly correlated with changes in inflammatory
markers, such as IL-6, IL-10, and CRP. Some types of chronic exercises
can reduce plasma FFA (Henderson, 2021), and long-term exercise has
an anti-inflammatory effect on adipose tissues (Metsios et al., 2020). A
study found that exercise can reduce liver inflammation by increasing
liver SIRT1 activity and promoting the deacetylation of NF-κB and PGC-
1α (Bianchi et al., 2021; Liu and Chang, 2018). A three-month study
showed that exercise can inhibit the production of pro-inflammatory
cytokines, such as IL-6 and TNF- α, reduce inflammation, and thus
prevent further damage to β-cells (El-Kader et al., 2014). We speculated
that six months of exercise may reduce plasma FFA and inflammatory
factors in older adults with PDM, and these changes are associated with
IHL. Our results showed that FFA did not change substantially possibly
because the FFA of the older adults was in the normal range before
intervention. After the intervention, we did not observe decreases in the
levels of inflammatory factors, especially IL-6 and TNF-α showed an
increasing trend. This result was not consistent with the expected re­
sults. The possible explanation may be that our conclusion was based on
the measurement of inflammatory regulatory factors in peripheral
blood. These results do not necessarily reflect the inflammatory state of
liver tissues (Bianchi et al., 2021). We did not control the level of sys­
temic or tissue-specific inflammation in different individuals before the
start of the experiment, which may have affected the results of the study.
Moreover, the role of IL-6 in metabolism is still controversial. Although
IL-6 is often considered a proinflammatory cytokine, muscle-derived IL-
6 has anti-inflammatory effects, and it can be released into the blood by
contractile skeletal muscle fibers during exercise (Pedersen and Fischer,
2007). IL-6 level increases during exercise, and if systemic changes are
to be detected, long-term and intense exercises involving large muscle
groups are required (Karstoft and Pedersen, 2016). Exercise training
may have a variety of potential stimulating effects on inflammatory
factors, such as IL-6, and its potential mechanism is not completely clear.
The strengths of our study include good adherence to exercise pro­
grams in older adults, direct supervision of all exercise training sessions,
and the use of advanced methods such as dual-energy x-ray and MRI
techniques to measure body fat content and IHL. This study also has
some limitations. First, the target population of our study is mainly the
Chinese middle-aged and elderly people, and whether or not similar
6
Experimental Gerontology 179 (2023) 112250
results will be observed in people of other races and ages is unclear.
Second, our preliminary result is IHL content rather than fibrosis or
steatosis confirmed by biopsy. Nevertheless, IHL content measured by
MRI is highly repeatable and is related to the histological characteristics
of fibrosis and steatosis (Zhang et al., 2016). Exercising together may
prevent some elderly people from getting adequate exercise. Thus, for an
improved personalized fitness effect, individuals should monitor exer­
cise intensity according to their situations. Notably, most of the older
adults in the exercise group have completed the exercise plan for six
months as required and have a high degree of enthusiasm. A possible
reason is that compared with other forms of aerobic exercise, Yijinjing
has lower requirements for the cardiopulmonary system and is more
easily accepted by the elderly. Our study is therefore well suited for
replication in older adults with poor motor ability. In addition, the
elastic band resistance exercise we selected has no requirements for
playgrounds. After the intervention, we conducted a follow-up survey
and found that most of the members of the exercise group have main­
tained their exercise habits.
5. Conclusion
In conclusion, in middle-aged and elderly people with PDM, six-
month Yijinjing combined with resistance exercise can reduce IHL;
decrease fat mass in the upper limbs, thighs, android area, gynoid area,
and whole-body; and improve FBG and IR. The benefits of Yijinjing plus
elastic band resistance training on the reduction of IHL may be related to
the reduction of weight, TC and HOMA-IR. This exercise has higher
compliance and is suitable for promotion and application in the middle-
aged and elderly people. However, for better prevention of T2DM,
continuous monitoring of exercise intensity and duration and caloric
intake restriction may be required.
CRediT authorship contribution statement
YWC participated in conception and design, participants ‘recruit­
ment, data collection, analysis and interpretation, statistical analysis,
and manuscript writing; SJW participated in participants ‘recruitment,
data collection and revised the manuscript for important intellectual
content; SSW participated in participants’ recruitment, data collection
and interpretation; QG contributed to data reduction and analysis,
interpretation of results; YDH,JYL participated in participants ‘recruit­
ment, data collection; RW contributed to the design of the study and
data analysis; XYL participated in the design of the study, data analysis
and interpretation, and manuscript revision; All authors have read and
approved the final version of the manuscript, and agree with the order of
presentation of the author.
Declaration of competing interest
The authors declare that they have no known competing financial
interests or personal relationships that could have appeared to influence
the work reported in this paper.
Acknowledgment
This study was supported by Key Laboratory of Exercise and Health
Sciences (Shanghai University of Sport), Shanghai Frontiers Science
Research Base of Exercise and Metabolic Health. The authors are
thankful to the local medical personnel from Shidong Hospital, for the
assistance with the study; and all the participants who participated in
this study. Funding source had no involvement in study design; in the
collection, analysis and interpretation of data; in the writing of the
report; and in the decision to submit the article for publication.
Y. Cai et al.
Funding sources
This study was supported by the Shanghai Local University Capacity
Project (STCSM#:23010504500).
Ethical statement
The study follows the principles of the Declaration of Helsinki. This
study was approved by the Ethics Committee of the Shanghai University
of Sport (Ref. No.: 102772021RT066). Informed consent will be ob­
tained from all participants.
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