Existing epidemiologic and clinical studies have demonstrated that obesity is associated with the risk of a variety of cancers. In recent years, an increasing number of experimental and clinical studies have unraveled the complex relationship between obesity and cancer risk and the underlying mechanisms. Obesity-induced abnormalities in immunity and biochemical metabolism, including chronic inflammation, hormonal disorders, dysregulation of adipokines, and microbial dysbiosis, may be important contributors to cancer development and progression. These contributors play different roles in cancer development and progression at different sites. Lifestyle changes, weight loss medications, and bariatric surgery are key approaches for weight-centered, obesity-related cancer prevention. Treatment of obesity-related inflammation and hormonal or metabolic dysregulation with medications has also shown promise in preventing obesity-related cancers. In this review, we summarize the mechanisms through which obesity affects the risk of cancer at different sites and explore intervention strategies for the prevention of obesity-associated cancers, concluding with unresolved questions and future directions regarding the link between obesity and cancer. The aim is to provide valuable theoretical foundations and insights for the in-depth exploration of the complex relationship between obesity and cancer risk and its clinical applications.
Humans ; Adipokines/metabolism* ; Bariatric Surgery ; Inflammation/therapy* ; Neoplasms/prevention & control* ; Obesity/therapy* ; Risk Factors

OBJECTIVE: To investigate the protective effects of modified Linggui Zhugan Decoction (, MLZD), a traditional Chinese medicine formula, on obese type 2 diabetes mellitus (T2DM) rats. METHODS: Fifty Sprague-Dawley rats were randomly divided into 5 groups by a random number table, including normal, obese T2DM (ob-T2DM), MLZD low-dose [MLDZ-L, 4.625 g/(kg·d)], MLZD middle-dose [MLD-M, 9.25 g/(kg·d) ] and MLZD high-dose [MLD-H, 18.5 g/(kg·d)] groups, 10 rats in each group. After 4-week intervention, blood samples and liver, pancreas, muscle tissues were collected to assess the insulin resistance (IR), blood lipid, adipokines and inflammation cytokines. The alteration of phosphatidylinositol 3 kinase (PI3K)-protein kinase B (PKB or Akt)/the mammalian target of rapamycin (mTOR)-ribosome protein subunit 6 kinase 1 (S6K1 )/AMP-activated protein kinase (AMPK)-peroxisome proliferator-activated receptor gamma coactivator 1 alpha (PGC-1 α) pathways were also studied. RESULTS: MLZD dose-dependently reduced fasting blood glucose, fasting insulin, homeostasis model of assessment for IR index and increased insulin sensitive index compared with ob-T2DM rats (P<0.05). Similarly, total cholesterol, triglyceride, low-density lipoprotein cholesterol and free fatty acids were also decreased compared with ob-T2DM rats after 4-week treatment (P<0.05 or P<0.01). Improvements in adipokines and inflammatory cytokines were observed with a raised level of adiponectin and a reduced level of leptin, resistin, tumor necrosis factor-α and interleukin-6 (P<0.05 or P<0.01). MLZD regulated the PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways and restored the tissue structure of liver and pancreas (P<0.05 or P<0.01). CONCLUSIONS MLZD ameliorated glycolipid metabolism and inflammation, which may be attributed to the regulation of PI3K-Akt/mTOR-S6K1/AMPK-PGC-1 α pathways.
AMP-Activated Protein Kinases/metabolism* ; Animals ; Diabetes Mellitus, Experimental ; Diabetes Mellitus, Type 2/drug therapy* ; Glycolipids ; Inflammation ; Obesity/drug therapy* ; Phosphatidylinositol 3-Kinases/metabolism* ; Proto-Oncogene Proteins c-akt/metabolism* ; Rats ; Rats, Sprague-Dawley ; Signal Transduction ; TOR Serine-Threonine Kinases/metabolism*

OBJECTIVE: To assess the efficacy of the combined treatment with electroacupuncture (EA) and intradermal needling on simple obesity and explore its underlying effect mechanism. METHODS: A total number of 116 patients with simple obesity were randomized into an observation group (58 cases, 3 cases dropped off and 2 cases removed) and a control group (58 cases, 4 cases dropped off and 1 cases removed). Patients in the control group received EA at Zhongwan (CV 12), Quchi (LI 11), Zusanli (ST 36), Pishu (BL 20), Weishu (BL 21), etc., for 30 min each time. On the base of the intervention as the control group, the patients in the observation group received the intradermal needling at Tianshu (ST 25), Daheng (SP 15), Zusanli (ST 36), Shangjuxu (ST 37), Quchi (LI 11), Pishu (BL 20) and Weishu (BL 21). In each group, the intervention was given once every two days, 3 times a week, consecutively for 3 months. Before and after treatment, the obesity indexes (body mass [BW], body mass index [BMI], body fat percentage [F%], adiposity [A] and waist circumference [WC]), the serum intestinal lymphatic function-related factors (vascular endothelial growth factor C [VEGF-C], delta-like ligand 4 [DLL4], adrenomedullin [ADM]), blood lipid (total cholesterol [TC], triglyceride [TG] and low density lipoprotein-cholesterol [LDL-C]), and fasting plasma glucose (FPG), fasting insulin (FINS) and insulin resistance index (HOMA-IR) were observed in the patients of both groups; and the efficacy was assessed. RESULTS: The effective rate was 88.7% (47/53) in the observation group, higher than 71.7% (38/53) in the control group (P<0.05). After treatment, except FPG in the control group, BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, as well as TC, TG, LDL-C, FBG, FINS and HOMA-IR were all reduced compared with those before treatment in both groups (P<0.05). The reduction ranges of BW, BMI, F%, A, WC, and the concentrations of serum VEGF-C, DLL4 and ADM, and TC, LDL-C, FINS and HOMA-IR in the observation group were all larger than those in the control group (P<0.05). CONCLUSION Electroacupuncture combined with intradermal needling can reduce body weight and lipid, and improve insulin resistance in treatment of simple obesity, which is achieved probably through inhibiting lymphangiogenesis and promoting lymphatic endothelial permeability.
Acupuncture Points ; Blood Glucose/metabolism* ; Cholesterol, LDL ; Electroacupuncture ; Humans ; Insulin Resistance ; Intestines ; Lipids ; Lymphocytes ; Obesity/therapy* ; Obesity, Morbid ; Triglycerides ; Vascular Endothelial Growth Factor C

Peptide dual agonists toward both glucagon-like peptide 1 receptor (GLP-1R) and glucagon receptor (GCGR) are emerging as novel therapeutics for the treatment of type 2 diabetes mellitus (T2DM) patients with obesity. Our previous work identified a Xenopus GLP-1-based dual GLP-1R/GCGR agonist termed xGLP/GCG-13, which showed decent hypoglycemic and body weight lowering activity. However, the clinical utility of xGLP/GCG-13 is limited due to its short in vivo half-life. Inspired by the fact that O-GlcNAcylation of intracellular proteins leads to increased stability of secreted proteins, we rationally designed a panel of O-GlcNAcylated xGLP/GCG-13 analogs as potential long-acting GLP-1R/ GCGR dual agonists. One of the synthesized glycopeptides 1f was found to be equipotent to xGLP/GCG-13 in cell-based receptor activation assays. As expected, O-GlcNAcylation effectively improved the stability of xGLP/GCG-13 in vivo. Importantly, chronic administration of 1f potently induced body weight loss and hypoglycemic effects, improved glucose tolerance, and normalized lipid metabolism and adiposity in both db/db and diet induced obesity (DIO) mice models. These results supported the hypothesis that glycosylation is a useful strategy for improving the in vivo stability of GLP-1-based peptides and promoted the development of dual GLP-1R/GCGR agonists as antidiabetic/antiobesity drugs.
Mice ; Animals ; Glucagon-Like Peptide 1/metabolism* ; Receptors, Glucagon/therapeutic use* ; Xenopus laevis/metabolism* ; Diabetes Mellitus, Type 2/drug therapy* ; Glycopeptides/therapeutic use* ; Obesity/drug therapy* ; Hypoglycemic Agents/pharmacology* ; Peptides/pharmacology*

OBJECTIVE: We aimed to explore how fermented barley extracts with Lactobacillus plantarum dy-1 (LFBE) affected the browning in adipocytes and obese rats. METHODS: In vitro, 3T3-L1 cells were induced by LFBE, raw barley extraction (RBE) and polyphenol compounds (PC) from LFBE to evaluate the adipocyte differentiation. In vivo, obese SD rats induced by high fat diet (HFD) were randomly divided into three groups treated with oral gavage: (a) normal control diet with distilled water, (b) HFD with distilled water, (c) HFD with 800 mg LFBE/kg body weight (bw). RESULTS: In vitro, LFBE and the PC in the extraction significantly inhibited adipogenesis and potentiated browning of 3T3-L1 preadipocytes, rather than RBE. In vivo, we observed remarkable decreases in the body weight, serum lipid levels, white adipose tissue (WAT) weights and cell sizes of brown adipose tissues (BAT) in the LFBE group after 10 weeks. LFBE group could gain more mass of interscapular BAT (IBAT) and promote the dehydrogenase activity in the mitochondria. And LFBE may potentiate process of the IBAT thermogenesis and epididymis adipose tissue (EAT) browning via activating the uncoupling protein 1 (UCP1)-dependent mechanism to suppress the obesity. CONCLUSION These results demonstrated that LFBE decreased obesity partly by increasing the BAT mass and the energy expenditure by activating BAT thermogenesis and WAT browning in a UCP1-dependent mechanism.
3T3 Cells ; Adipocytes ; drug effects ; physiology ; Adipose Tissue, Brown ; drug effects ; physiology ; Adipose Tissue, White ; drug effects ; physiology ; Animal Feed ; analysis ; Animals ; Anti-Obesity Agents ; administration & dosage ; metabolism ; Cell Differentiation ; drug effects ; Diet ; Fermentation ; Hordeum ; chemistry ; Lactobacillus plantarum ; chemistry ; Male ; Mice ; Obesity ; drug therapy ; genetics ; Plant Extracts ; chemistry ; Probiotics ; administration & dosage ; metabolism ; Random Allocation ; Rats ; Rats, Sprague-Dawley ; Uncoupling Protein 1 ; genetics ; metabolism

Globally, the problem of obesity is increasing, and the prevalence of obesity in Korea is also rising rapidly. Obesity is a risk factor for cardiometabolic diseases including type 2 diabetes mellitus, hypertension, cardiovascular disease, and some types of cancer. Therefore, prevention of various metabolic diseases or symptom relief through effective treatment of obesity is a very important problem. According to the obesity guidelines of the Obesity Society of Korea in 2018, obesity medication is recommended for patients with a body mass index (BMI) of 30 kg/m² or more or a BMI of 27 kg/m² or more, and one or more obesity accompanying diseases (type 2 diabetes, hypertension, dyslipidemia). In this case, it is recommended that the basic treatment for obesity (diet, exercise, and behavior therapy) should be performed in parallel with Saxenda® treatment. The glucagon-like peptide 1 analogue, Saxenda®, has been validated as a long-term effective and safe treatment for obesity, and is expected to be a promising drug for the treatment of obesity and the prevention of pre-diabetes in the future. However, in Korea, where non-standard obesity treatments are widely practiced, it is necessary to improve the health of obese patients by being treated with Saxenda® along with diet, exercise and behavior therapy.
Behavior Therapy ; Body Mass Index ; Cardiovascular Diseases ; Diabetes Mellitus ; Diabetes Mellitus, Type 2 ; Diet ; Glucagon-Like Peptide 1 ; Humans ; Hypertension ; Korea ; Metabolic Diseases ; Metabolism ; Obesity ; Prevalence ; Risk Factors ; Specialization

OBJECTIVETo study the protective effect of lipoxin A4 (LXA4) against sepsis induced by lipopolysaccharide (LPS) in rats with obesity and its effect on the expression of Toll-like receptor 4 (TLR4) and TNF receptor-associated factor 6 (TRAF6) in the liver.

METHODSA total of 60 male Sprague-Dawley rats aged three weeks were randomly divided into a normal group and an obesity group, with 30 rats in each group. A rat model of obesity was established by high-fat diet. Each of the two groups was further randomly divided into control group, sepsis group, and LXA4 group, and 8 rats were selected from each group. The rats in the control, sepsis, and LXA4 groups were treated with intraperitoneal injection of normal saline, LPS, and LXA4+LPS respectively. Twelve hours later, blood samples were collected from the heart and liver tissue samples were also collected. ELISA was used to measure the serum levels of interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α). Western blot was used to measure the protein expression of TLR4 and TRAF6 in liver tissue. Quantitative real-time PCR was used to measure the mRNA expression of TLR4 and TRAF6.

RESULTSAfter being fed with high-fat diet for 6 weeks, the obesity group had significantly higher average weight and Lee's index than the normal group (P<0.05). Compared with the normal group, the obesity group had significant increases in the serum levels of IL-6 and TNF-α (P<0.05). In the normal group or the obesity group, the sepsis subgroup had significant increases in the serum levels of IL-6 and TNF-α compared with the control subgroup (P<0.05), while the LXA4 subgroup had significant reductions in the two indices compared with the sepsis subgroup (P<0.05). Compared with the normal group, the obesity group had significant increases in the protein and mRNA expression of TLR4 and TRAF6 (P<0.05). In the normal group or the obesity group, the sepsis subgroup had significant increases in the protein and mRNA expression of TLR4 and TRAF6 compared with the control subgroup (P<0.05). Compared with the sepsis subgroup, the LXA4 subgroup had significant reductions in the protein and mRNA expression of TLR4 and TRAF6 (P<0.05).

CONCLUSIONSLXA4 can reduce the serum levels of IL-6 and TNF-α and alleviate inflammatory response. LXA4 can inhibit the expression of TLR4 and TRAF6 in the liver of septic rats, possibly by inhibiting the TLR4 signaling pathway.

Animals ; Humans ; Interleukin-6 ; genetics ; metabolism ; Lipoxins ; administration & dosage ; Liver ; drug effects ; metabolism ; Male ; Obesity ; complications ; drug therapy ; genetics ; metabolism ; Rats ; Rats, Sprague-Dawley ; Sepsis ; complications ; drug therapy ; genetics ; metabolism ; Signal Transduction ; drug effects ; TNF Receptor-Associated Factor 6 ; genetics ; metabolism ; Toll-Like Receptor 4 ; genetics ; metabolism ; Tumor Necrosis Factor-alpha ; genetics ; metabolism

Postmenopausal women, who have reduced circulating estrogen levels, are more prone to develop obesity and related metabolic diseases than premenopausal women. The absence of safe and effective treatments for postmenopausal obesity has changed the focus to natural products as alternative remedies. Total salvianolic acids (TSA) are the major water-soluble ingredients of Danshen. Salvianolic acid (SA) is the major constituent of the TSA. Salvianolic acids, including TSA and SA, are widely used in traditional Chinese medicine. In the present study, ovariectomized rats and LO2 cells were used to study the effects of salvianolic acids on body weight gain and hepatic steatosis. Salvianolic acids reduced ovariectomy (OVX)-induced body weight gain, attenuated the expressions of hepatic lipogenic genes, such as sterol regulatory element binding protein (SREBP)1, fatty acid synthase (FAS), and stearoyl-CoA desaturase (SCD)1, and decreased the liver triglyceride (TG) and total cholesterol (TC). For the molecular mechanisms, OVX and high glucose-induced phosphorylation of signal transducer and activator of transcription (STAT)-3 was inhibited by salvianolic acids treatment. In LO2 cells, inhibition of STAT-3 by siRNA attenuated the increased expression of SREBP1 and TG induced by high glucose. Salvianolic acids reduced the upregulation of SREBP1 and TG induced by high glucose in LO2 cells. In conclusion, these findings illustrated that salvianolic acids markedly alleviated the lipid metabolism disorders and protected against the postmenopausal obesity. The underlying mechanism was probably associated with the regulation of STAT-3 signaling.
Alkenes ; administration & dosage ; Animals ; Drugs, Chinese Herbal ; administration & dosage ; Female ; Humans ; Lipid Metabolism ; drug effects ; Liver ; drug effects ; metabolism ; Obesity ; drug therapy ; genetics ; metabolism ; Ovariectomy ; Polyphenols ; administration & dosage ; Postmenopause ; drug effects ; genetics ; metabolism ; Rats ; STAT3 Transcription Factor ; genetics ; metabolism ; Salvia miltiorrhiza ; chemistry ; Signal Transduction ; drug effects ; Sterol Regulatory Element Binding Protein 1 ; genetics ; metabolism ; Triglycerides ; metabolism

OBJECTIVE: To investigate the effects of 4-week moderate aerobic exercise plus diet control on serum levels of total insulin-like growth factor 1(IGF-1) and IGF-1 binding protein-3 (IGFBP-3) as well as IGF-1 activity (reflected by molar ratio of IGF-1/IGFBP-3) in female obese adolescents and youths, and their possible role on fat loss, and improvement of glucose and lipid metabolism. METHODS: Nine female obese youths (age:18~19 y) and 30 female obese adolescents (age:14~16 y) were recruited and undertook 4-week aerobic exercise such as swimming and jogging (6 days/week, twice a day, 2 h/time with 5 min rest per 30 min exercise) with gradual increase of intensity from low (heart rate immediately post-exercise of 1st week:100~120 beats/min) to moderate (heart rate immediately post-exercise of 2-4 weeks:120~140 beats/min) level, combined with a diet intervention (total daily energy intake of 1 400 or 1 600 kcal according to basal metabolism rate) in Shanghai Dianfeng weight loss enclosed camp. Nine normal weight young women and 9 female children matched at age and nationality were recruited as the normal control. Before and after the experimental period, anthropometric index (body weight, body mass index(BMI) and waist circumference), glucose and lipid metabolism parameters including fasting blood glucose (FBG), fasting insulin (FINS), homeostasis model assessment of insulin resistance (HOMA-IR), triglyceride (TG); total cholesterol (TC), low density lipoprotein (LDL) and high density lipoprotein (HDL), and serum levels of total IGF-1 and IGFBP-3 were measured, and IGF-1 activity was calculated in the obese and normal control female adolescents. RESULTS: ①Compared with normal control, the serum levels of total IGF-1 and IGFBP-3 were decreased in the female obese youths and adolescents, and IGF-1 activity was reduced only in the obese female adolescents. ②The serum level of IGFBP-3 was down-regulated and IGF-1 activity was up-regulated while no change of serum total IGF-1 was induced by 4-week moderate aerobic exercise plus diet control, accompanied with significant decreases of body weight, BMI and waist circumference as well as improvement of glucose and lipid metabolism in the female obese youths and adolescents. Except for a positive association between the increased IGF-1 activity and the decreased waist circumference was found in the female obese youths by Pearson's correlation analysis, there was no relation of the decreased IGFBP-3, the increased IGF-1 activity with the improvements of anthropometric index and glucose and lipid metabolism in female obese youths and adolescents. CONCLUSIONS The serum level of IGFBP-3 was down-regulated and the IGF-1 activity was up-regulated by 4-week moderate aerobic exercise plus diet control in female obese youths and adolescents. The increase of IGF-1 activity might be associated with the exercise-plus-diet-induced decrease of waist circumstance in female obese youths.
Adolescent ; Blood Glucose ; China ; Diet, Reducing ; Exercise ; Female ; Humans ; Insulin ; blood ; Insulin-Like Growth Factor Binding Protein 3 ; metabolism ; Insulin-Like Growth Factor I ; metabolism ; Pediatric Obesity ; therapy ; Young Adult

BACKGROUNDObesity has an adverse effect on iron status. Hepcidin-mediated inhibition of iron absorption in the duodenum is a potential mechanism. Iron-deficient obese patients have diminished response to oral iron therapy. This study was designed to assess whether acupuncture could promote the efficacy of oral iron supplementation for the treatment of obesity-related iron deficiency (ID).

METHODSSixty ID or ID anemia (IDA) patients with obesity were screened at Beijing Hospital of Traditional Chinese Medicine and were randomly allocated to receive either oral iron replacement allied with acupuncture weight loss treatment (acupuncture group, n = 30) or oral iron combined with sham-acupuncture treatment (control group, n = 30). Anthropometric parameters were measured and blood samples were tested pre- and post-treatment. Differences in the treatment outcomes of ID/IDA were compared between the two groups.

RESULTSAfter 8 weeks of acupuncture treatment, there was a significant decrease in body weight, body mass index, waist circumference, and waist/hip circumference ratio of patients in the acupuncture group, while no significant changes were observed in the control group. Oral iron supplementation brought more obvious improvements of iron status indicators including absolute increases in serum iron (11.08 ± 2.19 μmol/L vs. 4.43 ± 0.47 μmol/L), transferrin saturation (11.26 ± 1.65% vs. 1.01 ± 0.23%), and hemoglobin (31.47 ± 1.19 g/L vs. 21.00 ± 2.69 g/L) in the acupuncture group than control group (all P < 0.05). Meanwhile, serum leptin (2.26 ± 0.45 ng/ml vs. 8.13 ± 0.55 ng/ml, P < 0.05) and hepcidin (3.52 ± 1.23 ng/ml vs. 6.77 ± 0.84 ng/ml, P < 0.05) concentrations declined significantly in the acupuncture group than those in the control group.

CONCLUSIONAcupuncture-based weight loss can enhance the therapeutic effects of iron replacement therapy for obesity-related ID/IDA through improving intestinal iron absorption, probably by downregulating the systemic leptin-hepcidin levels.

Acupuncture Therapy ; Adult ; Female ; Hepcidins ; blood ; Humans ; Intestinal Absorption ; physiology ; Iron ; deficiency ; metabolism ; Leptin ; blood ; Male ; Middle Aged ; Obesity ; blood ; metabolism ; therapy ; Young Adult