β-Hydroxybutyrate is reduced in humans with obesity-related NAFLD and displays a dose-dependent effect on skeletal muscle mitochondrial respiration in vitro

Nonalcoholic fatty liver disease (NAFLD) is characterized by hepatic fat accumulation and impaired insulin sensitivity. Reduced hepatic ketogenesis may promote these pathologies, but data are inconclusive in humans and the link between NAFLD and reduced insulin sensitivity remains obscure. We investigated individuals with obesity-related NAFLD and hypothesized that β-hydroxybutyrate (βOHB; the predominant ketone species) would be reduced and related to hepatic fat accumulation and insulin sensitivity. Furthermore, we hypothesized that ketones would impact skeletal muscle mitochondrial respiration in vitro. Hepatic fat was assessed by 1H-MRS in 22 participants in a parallel design, case control study [Control: n = 7, age 50 ± 6 yr, body mass index (BMI) 30 ± 1 kg/m2; NAFLD: n = 15, age 57 ± 3 yr, BMI 35 ± 1 kg/m2]. Plasma assessments were conducted in the fasted state. Whole body insulin sensitivity was determined by the gold-standard hyperinsulinemic-euglycemic clamp. The effect of ketone dose (0.5–5.0 mM) on mitochondrial respiration was conducted in human skeletal muscle cell culture. Fasting βOHB, a surrogate measure of hepatic ketogenesis, was reduced in NAFLD (−15.6%, P < 0.01) and correlated negatively with liver fat ( r2 = 0.21, P = 0.03) and positively with insulin sensitivity ( r2 = 0.30, P = 0.01). Skeletal muscle mitochondrial oxygen consumption increased with low-dose ketones, attributable to increases in basal respiration (135%, P < 0.05) and ATP-linked oxygen consumption (136%, P < 0.05). NAFLD pathophysiology includes impaired hepatic ketogenesis, which is associated with hepatic fat accumulation and impaired insulin sensitivity. This reduced capacity to produce ketones may be a potential link between NAFLD and NAFLD-associated reductions in whole body insulin sensitivity, whereby ketone concentrations impact skeletal muscle mitochondrial respiration.

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Acquired obesity is associated with increased liver fat, intra-abdominal fat, and insulin resistance in young adult monozygotic twins

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00381.2004 ◽

2005 ◽

Vol 288 (4) ◽

pp. E768-E774 ◽

Cited By ~ 63

Author(s):

Kirsi Hannele Pietiläinen ◽

Aila Rissanen ◽

Jaakko Kaprio ◽

Sari Mäkimattila ◽

Anna-Maija Häkkinen ◽

...

Keyword(s):

Insulin Resistance ◽

Insulin Sensitivity ◽

Monozygotic Twins ◽

Fat Distribution ◽

Population Based ◽

Abdominal Fat ◽

Liver Fat ◽

Whole Body ◽

Fasting Insulin ◽

Impaired Insulin

We determined whether acquired obesity is associated with increases in liver or intra-abdominal fat or impaired insulin sensitivity by studying monozygotic (MZ) twin pairs discordant and concordant for obesity. We studied nineteen 24- to 27-yr-old MZ twin pairs, with intrapair differences in body weight ranging from 0.1 to 24.7 kg [body mass index (BMI) range 20.0–33.9 kg/m2], identified from a population-based FinnTwin16 sample. Fat distribution was determined by magnetic resonance imaging, percent body fat by dual-energy X-ray absorptiometry, liver fat by proton spectroscopy, insulin sensitivity by measuring the fasting insulin concentration, and whole body insulin sensitivity by the euglycemic insulin clamp technique. Intrapair differences in BMI were significantly correlated with those in intra-abdominal fat ( r = 0.82, P < 0.001) and liver fat ( r = 0.57, P = 0.010). Intrapair differences in fasting insulin correlated with those in subcutaneous abdominal ( r = 0.60, P = 0.008), intra-abdominal ( r = 0.75, P = 0.0001) and liver ( r = 0.49, P = 0.048) fat. Intrapair differences in whole body insulin sensitivity correlated with those in subcutaneous abdominal ( r = −0.72, P = 0.001) and intra-abdominal ( r = −0.55, P = 0.015) but not liver ( r = −0.20, P = 0.20) fat. We conclude that acquired obesity is associated with increases in intra-abdominal and liver fat and insulin resistance, independent of genetic factors.

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Exercise training improves mitochondrial respiration and is associated with an altered intramuscular phospholipid signature in women with obesity

Diabetologia ◽

10.1007/s00125-021-05430-6 ◽

2021 ◽

Author(s):

Amy E. Mendham ◽

Julia H. Goedecke ◽

Yingxu Zeng ◽

Steen Larsen ◽

Cindy George ◽

...

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Exercise Training ◽

Protein Content ◽

Mitochondrial Respiration ◽

Controlled Trial ◽

Peak Oxygen Consumption ◽

Whole Body ◽

Post Intervention ◽

Sphingomyelin Synthase

Abstract Aims/hypothesis We sought to determine putative relationships among improved mitochondrial respiration, insulin sensitivity and altered skeletal muscle lipids and metabolite signature in response to combined aerobic and resistance training in women with obesity. Methods This study reports a secondary analysis of a randomised controlled trial including additional measures of mitochondrial respiration, skeletal muscle lipidomics, metabolomics and protein content. Women with obesity were randomised into 12 weeks of combined aerobic and resistance exercise training (n = 20) or control (n = 15) groups. Pre- and post-intervention testing included peak oxygen consumption, whole-body insulin sensitivity (intravenous glucose tolerance test), skeletal muscle mitochondrial respiration (high-resolution respirometry), lipidomics and metabolomics (mass spectrometry) and lipid content (magnetic resonance imaging and spectroscopy). Proteins involved in glucose transport (i.e. GLUT4) and lipid turnover (i.e. sphingomyelin synthase 1 and 2) were assessed by western blotting. Results The original randomised controlled trial showed that exercise training increased insulin sensitivity (median [IQR]; 3.4 [2.0–4.6] to 3.6 [2.4–6.2] x10−5 pmol l−1 min−1), peak oxygen consumption (mean ± SD; 24.9 ± 2.4 to 27.6 ± 3.4 ml kg−1 min−1), and decreased body weight (84.1 ± 8.7 to 83.3 ± 9.7 kg), with an increase in weight (pre intervention, 87.8± 10.9 to post intervention 88.8 ± 11.0 kg) in the control group (interaction p < 0.05). The current study shows an increase in mitochondrial respiration and content in response to exercise training (interaction p < 0.05). The metabolite and lipid signature at baseline were significantly associated with mitochondrial respiratory capacity (p < 0.05) but were not associated with whole-body insulin sensitivity or GLUT4 protein content. Exercise training significantly altered the skeletal muscle lipid profile, increasing specific diacylglycerol(32:2) and ceramide(d18:1/24:0) levels, without changes in other intermediates or total content of diacylglycerol and ceramide. The total content of cardiolipin, phosphatidylcholine (PC) and phosphatidylethanolamine (PE) increased with exercise training with a decrease in the PC:PE ratios containing 22:5 and 20:4 fatty acids. These changes were associated with content-driven increases in mitochondrial respiration (p < 0.05), but not with the increase in whole-body insulin sensitivity or GLUT4 protein content. Exercise training increased sphingomyelin synthase 1 (p < 0.05), with no change in plasma-membrane-located sphingomyelin synthase 2. Conclusions/interpretation The major findings of our study were that exercise training altered specific intramuscular lipid intermediates, associated with content-driven increases in mitochondrial respiration but not whole-body insulin sensitivity. This highlights the benefits of exercise training and presents putative target pathways for preventing lipotoxicity in skeletal muscle, which is typically associated with the development of type 2 diabetes. Graphical abstract

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Astragalus Polysaccharide Suppresses Skeletal Muscle Myostatin Expression in Diabetes: Involvement of ROS-ERK and NF-κB Pathways

Oxidative Medicine and Cellular Longevity ◽

10.1155/2013/782497 ◽

2013 ◽

Vol 2013 ◽

pp. 1-10 ◽

Cited By ~ 19

Author(s):

Min Liu ◽

Jian Qin ◽

Yarong Hao ◽

Min Liu ◽

Jun Luo ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

Saturated Acid ◽

C2c12 Cells ◽

Whole Body ◽

Protective Effects ◽

Kkay Mice ◽

Astragalus Polysaccharide

Objective. The antidiabetes drug astragalus polysaccharide (APS) is capable of increasing insulin sensitivity in skeletal muscle and improving whole-body glucose homeostasis. Recent studies suggest that skeletal muscle secreted growth factor myostatin plays an important role in regulating insulin signaling and insulin resistance. We hypothesized that regulation of skeletal muscle myostatin expression may be involved in the improvement of insulin sensitivity by APS.Methods. APS was administered to 13-week-old diabetic KKAy and nondiabetic C57BL/6J mice for 8 weeks. Complementary studies examined APS effects on the saturated acid palmitate-induced insulin resistance and myostatin expression in C2C12 cells.Results. APS treatment ameliorated hyperglycemia, hyperlipidemia, and insulin resistance and decreased the elevation of myostatin expression and malondialdehyde production in skeletal muscle of noninsulin-dependent diabetic KKAy mice. In C2C12 cells in vitro, saturated acid palmitate-induced impaired glucose uptake, overproduction of ROS, activation of extracellular regulated protein kinases (ERK), and NF-κB were partially restored by APS treatment. The protective effects of APS were mimicked by ERK and NF-κB inhibitors, respectively.Conclusion. Our study demonstrates elevated myostatin expression in skeletal muscle of type 2 diabetic KKAy mice and in cultured C2C12 cells exposed to palmitate. APS is capable of improving insulin sensitivity and decreasing myostatin expression in skeletal muscle through downregulating ROS-ERK-NF-κB pathway.

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A single intake of capsiate improves mechanical performance and bioenergetics efficiency in contracting mouse skeletal muscle

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.00520.2013 ◽

2014 ◽

Vol 306 (10) ◽

pp. E1110-E1119 ◽

Cited By ~ 8

Author(s):

Yashiro Kazuya ◽

Anne Tonson ◽

Emilie Pecchi ◽

Christiane Dalmasso ◽

Christophe Vilmen ◽

...

Keyword(s):

Skeletal Muscle ◽

Oxidative Phosphorylation ◽

Mitochondrial Respiration ◽

Mechanical Performance ◽

Uncoupling Protein ◽

Muscle Performance ◽

Whole Body ◽

Resonance Spectroscopy ◽

Twitch Force

Capsiate is known to increase whole body oxygen consumption possibly via the activation of uncoupling processes, but its effect at the skeletal muscle level remains poorly documented and conflicting. To clarify this issue, gastrocnemius muscle function and energetics were investigated in mice 2 h after a single intake of either vehicle (control) or purified capsiate (at 10 or 100 mg/kg body wt) through a multidisciplinary approach combining in vivo and in vitro measurements. Mechanical performance and energy pathway fluxes were assessed strictly noninvasively during a standardized electrostimulation-induced exercise, using an original device implementing 31-phosphorus magnetic resonance spectroscopy, and mitochondrial respiration was evaluated in isolated saponin-permeabilized fibers. Compared with control, both capsiate doses produced quantitatively similar effects at the energy metabolism level, including an about twofold decrease of the mitochondrial respiration sensitivity for ADP. Interestingly, they did not alter either oxidative phosphorylation or uncoupling protein 3 gene expression at rest. During 6 min of maximal repeated isometric contractions, both doses reduced the amount of ATP produced from glycolysis and oxidative phosphorylation but increased the relative contribution of oxidative phosphorylation to total energy turnover (+28 and +21% in the 10- and 100-mg groups, respectively). ATP cost of twitch force generation was further reduced in the 10- (−35%) and 100-mg (−45%) groups. Besides, the highest capsiate dose also increased the twitch force-generating capacity. These data present capsiate as a helpful candidate to enhance both muscle performance and oxidative phosphorylation during exercise, which could constitute a nutritional approach for improving health and preventing obesity and associated metabolic disorders.

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Intramuscular Injection of miR-1 Reduces Insulin Resistance in Obese Mice

Frontiers in Physiology ◽

10.3389/fphys.2021.676265 ◽

2021 ◽

Vol 12 ◽

Author(s):

Alice C. Rodrigues ◽

Alexandre R. Spagnol ◽

Flávia de Toledo Frias ◽

Mariana de Mendonça ◽

Hygor N. Araújo ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Oxygen Consumption ◽

Insulin Sensitivity ◽

Mitochondrial Respiration ◽

High Fat Diet ◽

C2c12 Cells ◽

High Fat ◽

Spare Capacity

The role of microRNAs in metabolic diseases has been recognized and modulation of them could be a promising strategy to treat obesity and obesity-related diseases. The major purpose of this study was to test the hypothesis that intramuscular miR-1 precursor replacement therapy could improve metabolic parameters of mice fed a high-fat diet. To this end, we first injected miR-1 precursor intramuscularly in high-fat diet-fed mice and evaluated glucose tolerance, insulin sensitivity, and adiposity. miR-1-treated mice did not lose weight but had improved insulin sensitivity measured by insulin tolerance test. Next, using an in vitro model of insulin resistance by treating C2C12 cells with palmitic acid (PA), we overexpressed miR-1 and measured p-Akt content and the transcription levels of a protein related to fatty acid oxidation. We found that miR-1 could not restore insulin sensitivity in C2C12 cells, as indicated by p-Akt levels and that miR-1 increased expression of Pgc1a and Cpt1b in PA-treated cells, suggesting a possible role of miR-1 in mitochondrial respiration. Finally, we analyzed mitochondrial oxygen consumption in primary skeletal muscle cells treated with PA and transfected with or without miR-1 mimic. PA-treated cells showed reduced basal respiration, oxygen consumption rate-linked ATP production, maximal and spare capacity, and miR-1 overexpression could prevent impairments in mitochondrial respiration. Our data suggest a role of miR-1 in systemic insulin sensitivity and a new function of miR-1 in regulating mitochondrial respiration in skeletal muscle.

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Inducible Deletion of Protein Kinase Map4k4 in Obese Mice Improves Insulin Sensitivity in Liver and Adipose Tissues

Molecular and Cellular Biology ◽

10.1128/mcb.00150-15 ◽

2015 ◽

Vol 35 (13) ◽

pp. 2356-2365 ◽

Cited By ~ 15

Author(s):

Laura V. Danai ◽

Rachel J. Roth Flach ◽

Joseph V. Virbasius ◽

Lorena Garcia Menendez ◽

Dae Young Jung ◽

...

Keyword(s):

Skeletal Muscle ◽

Adipose Tissue ◽

Insulin Sensitivity ◽

Protein Kinase ◽

Insulin Signaling ◽

Fasting Blood Glucose ◽

Mitogen Activated Protein Kinase ◽

Whole Body ◽

Metabolic Phenotypes

Studiesin vitrosuggest that mitogen-activated protein kinase kinase kinase kinase 4 (Map4k4) attenuates insulin signaling, but confirmationin vivois lacking since Map4k4 knockout is lethal during embryogenesis. We thus generated mice with floxed Map4k4 alleles and a tamoxifen-inducible Cre/ERT2 recombinase under the control of the ubiquitin C promoter to induce whole-body Map4k4 deletion after these animals reached maturity. Tamoxifen administration to these mice induced Map4k4 deletion in all tissues examined, causing decreased fasting blood glucose concentrations and enhanced insulin signaling to AKT in adipose tissue and liver but not in skeletal muscle. Surprisingly, however, mice generated with a conditional Map4k4 deletion in adiponectin-positive adipocytes or in albumin-positive hepatocytes displayed no detectable metabolic phenotypes. Instead, mice with Map4k4 deleted in Myf5-positive tissues, including all skeletal muscles tested, were protected from obesity-induced glucose intolerance and insulin resistance. Remarkably, these mice also showed increased insulin sensitivity in adipose tissue but not skeletal muscle, similar to the metabolic phenotypes observed in inducible whole-body knockout mice. Taken together, these results indicate that (i) Map4k4 controls a pathway in Myf5-positive cells that suppresses whole-body insulin sensitivity and (ii) Map4k4 is a potential therapeutic target for improving glucose tolerance and insulin sensitivity in type 2 diabetes.

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Effect of training on insulin binding to rat skeletal muscle sarcolemmal vesicles

AJP Endocrinology and Metabolism ◽

10.1152/ajpendo.1986.250.5.e570 ◽

1986 ◽

Vol 250 (5) ◽

pp. E570-E575

Author(s):

G. K. Grimditch ◽

R. J. Barnard ◽

S. A. Kaplan ◽

E. Sternlicht

Keyword(s):

Skeletal Muscle ◽

Insulin Sensitivity ◽

Exercise Training ◽

Insulin Binding ◽

Whole Body ◽

Rat Skeletal Muscle ◽

Binding Studies ◽

Muscle Enzyme ◽

Intravenous Glucose ◽

High Affinity

We examined the hypothesis that the exercise training-induced increase in skeletal muscle insulin sensitivity is mediated by adaptations in insulin binding to sarcolemmal (SL) insulin receptors. Insulin binding studies were performed on rat skeletal muscle SL isolated from control and trained rats. No significant differences were noted between groups in body weight or fat. An intravenous glucose tolerance test showed an increase in whole-body insulin sensitivity with training, and specific D-glucose transport studies on isolated SL vesicles indicated that this was due in part to adaptations in skeletal muscle. Enzyme marker analyses revealed no differences in yield, purity, or contamination of SL membranes between the two groups. Scatchard analyses indicated no significant differences in the number of insulin binding sites per milligram SL protein on the high-affinity (15.0 +/- 4.1 vs. 18.1 +/- 6.4 X 10(9)) or on the low-affinity portions (925 +/- 80 vs. 884 +/- 106 X 10(9)) of the curves. The association constants of the high-affinity (0.764 +/- 0.154 vs. 0.685 +/- 0.264 X 10(9) M-1) and of the low affinity sites (0.0096 +/- 0.0012 vs. 0.0102 +/- 0.0012 X 10(9) M-1) also were similar. These results do not support the hypothesis that the increased sensitivity to insulin after exercise training is due to changes in SL insulin receptor binding.

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Alanine Aminotransferase Levels and Fatty Liver in Childhood Obesity: Associations with Insulin Resistance, Adiponectin, and Visceral Fat

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2006-1010 ◽

2006 ◽

Vol 91 (11) ◽

pp. 4287-4294 ◽

Cited By ~ 243

Author(s):

Tania S. Burgert ◽

Sara E. Taksali ◽

James Dziura ◽

T. Robin Goodman ◽

Catherine W. Yeckel ◽

...

Keyword(s):

Lipid Metabolism ◽

Insulin Sensitivity ◽

Fatty Liver ◽

Visceral Fat ◽

Resonance Imaging ◽

Fat Accumulation ◽

Glucose And Lipid Metabolism ◽

The Metabolic Syndrome ◽

Hepatic Fat ◽

Fat Fraction

Abstract Background: Concurrent with the rise in obesity, nonalcoholic fatty liver disease is recognized as the leading cause of serum aminotransferase elevations in obese youth. Nevertheless, the complete metabolic phenotype associated with abnormalities in biomarkers of liver injury and intrahepatic fat accumulation remains to be established. Methods: In a multiethnic cohort of 392 obese adolescents, alanine aminotransferase (ALT) levels were related with parameters of insulin sensitivity, glucose, and lipid metabolism as well as adipocytokines and biomarkers of inflammation. A subset of 72 adolescents had determination of abdominal fat partitioning and intrahepatic fat accumulation using magnetic resonance imaging. Findings: Elevated ALT (>35 U/liter) was found in 14% of adolescents, with a predominance of male gender and white/Hispanic race/ethnicity. After adjusting for potential confounders, rising ALT was associated with reduced insulin sensitivity and glucose tolerance as well as rising free fatty acids and triglycerides. Worsening of glucose and lipid metabolism was already evident as ALT levels rose into the upper half of the normal range (18–35 U/liter). When hepatic fat fraction was assessed using fast magnetic resonance imaging, 32% of subjects had an increased hepatic fat fraction, which was associated with decreased insulin sensitivity and adiponectin, and increased triglycerides, visceral fat, and deep to superficial sc fat ratio. The prevalence of the metabolic syndrome was significantly greater in those with fatty liver. Interpretation: Deterioration in glucose and lipid metabolism is associated even with modest ALT elevations. Hepatic fat accumulation in childhood obesity is strongly associated with the triad of insulin resistance, increased visceral fat, and hypoadiponectinemia. Hence, hepatic steatosis may be a core feature of the metabolic syndrome.

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Hepatokine ERAP1 impairs skeletal muscle insulin sensitivity via ADRB2/PKA pathway

10.21203/rs.3.rs-37586/v1 ◽

2020 ◽

Author(s):

Feifan Guo ◽

Yuguo Niu ◽

Haizhou Jiang ◽

Hanrui Yin ◽

Fenfen Wang ◽

...

Keyword(s):

Insulin Resistance ◽

Skeletal Muscle ◽

Insulin Sensitivity ◽

Neutralizing Antibodies ◽

Leptin Receptor ◽

Whole Body ◽

C2c12 Myotubes ◽

Insulin Resistant ◽

Skeletal Muscle Insulin Sensitivity ◽

Pka Pathway

Abstract The current study aimed to investigate the role of endoplasmic reticulum aminopeptidase 1 (ERAP1), a novel hepatokine, in whole-body glucose metabolism. Here, we found that hepatic ERAP1 levels were increased in insulin-resistant leptin-receptor-mutated (db/db) and high-fat diet (HFD)-fed mice. Consistently, hepatic ERAP1 overexpression attenuated skeletal muscle (SM) insulin sensitivity, whereas knockdown ameliorated SM insulin resistance. Furthermore, serum and hepatic ERAP1 levels were positively correlated, and recombinant mouse ERAP1 or conditioned medium with high ERAP1 content (CM-ERAP1) attenuated insulin signaling in C2C12 myotubes, and CM-ERAP1 or HFD-induced insulin resistance was blocked by ERAP1 neutralizing antibodies. Mechanistically, ERAP1 reduced ADRB2 expression and interrupted ADRB2-dependent signaling in C2C12 myotubes. Finally, ERAP1 inhibition via global knockout or the inhibitor thimerosal improved insulin sensitivity. Together, ERAP1 is a hepatokine that impairs SM and whole-body insulin sensitivity, and its inhibition might provide a therapeutic strategy for diabetes, particularly for those with SM insulin resistance.

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Short-term strength training reduces gluconeogenesis and NAFLD in obese mice

Journal of Endocrinology ◽

10.1530/joe-18-0567 ◽

2019 ◽

Vol 241 (1) ◽

pp. 59-70 ◽

Cited By ~ 8

Author(s):

Rodrigo Martins Pereira ◽

Kellen Cristina da Cruz Rodrigues ◽

Chadi Pellegrini Anaruma ◽

Marcella Ramos Sant’Ana ◽

Thaís Dantis Pereira de Campos ◽

...

Keyword(s):

Weight Loss ◽

Insulin Sensitivity ◽

Strength Training ◽

Term Strength ◽

Obese Mice ◽

Short Term ◽

Fat Accumulation ◽

Hepatic Insulin Sensitivity ◽

Short Term Strength ◽

Hepatic Fat

Non-alcoholic fatty liver disease (NAFLD) has a positive correlation with obesity, insulin resistance and type 2 diabetes mellitus (T2D). The aerobic training is an important tool in combating NAFLD. However, no studies have demonstrated the molecular effects of short-term strength training on the accumulation of hepatic fat in obese mice. This study aimed to investigate the effects of short-term strength training on the mechanisms of oxidation and lipid synthesis in the liver of obese mice. The short duration protocol was used to avoid changing the amount of adipose tissue. Swiss mice were separated into three groups: lean control (CTL), sedentary obese (OB) and strength training obese (STO). The obese groups were fed a high-fat diet (HFD) and the STO group performed the strength training protocol 1 session/day for 15 days. The short-term strength training reduced hepatic fat accumulation, increasing hepatic insulin sensitivity and controlling hepatic glucose production. The obese animals increased the mRNA of lipogenic genes Fasn and Scd1 and reduced the oxidative genes Cpt1a and Ppara. On the other hand, the STO group presented the opposite results. Finally, the obese animals presented higher levels of lipogenic proteins (ACC and FAS) and proinflammatory cytokines (TNF-α and IL-1β), but the short-term strength training was efficient in reducing this condition, regardless of body weight loss. In conclusion, there was a reduction of obesity-related hepatic lipogenesis and inflammation after short-term strength training, independent of weight loss, leading to improvements in hepatic insulin sensitivity and glycemic homeostasis in obese mice. Key points: (1) Short-term strength training (STST) reduced fat accumulation and inflammation in the liver; (2) Hepatic insulin sensitivity and HPG control were increased with STST; (3) The content and activity of ACC and content of FAS were reduced with STST; (4) STST improved hepatic fat accumulation and glycemic homeostasis; (5) STST effects were observed independently of body weight change.

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