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Journal of Obesity & Metabolic Syndrome.2024;33(4):289-301. doi:10.7570/jomes24035

The core pathophysiology of polycystic ovary syndrome involves an overproduction of androgens primarily originating from ovarian thecal cells. Two major external triggers promote androgen overproduction in the ovaries: the increased secretion of luteinizing hormone, a consequence of aberrant hypothalamic gonadotropin-releasing hormone secretion dynamics, and compensatory hyperinsulinemia resulting from insulin resistance.Obesity interacts with polycystic ovary syndrome in multiple ways, but a major role of obesity in its pathophysiology is the exacerbation of insulin resistance. Additionally, obesity contributes to polycystic ovary syndrome by facilitating the conversion of precursor hormones to testosterone within adipose cells. Moreover, obesity can lead to relative hyperandrogenemia, which is marked by lower levels of sex hormone binding globulin and increased availability of free testosterone to target tissues. Also, obesity affects the secretion of gonadotropins, resulting in heightened luteinizing hormone secretion or increased sensitivity of thecal cells to luteinizing hormone. Obesity-related insulin resistance might be amplified by alterations in adipokine and inflammatory cytokine production. Ultimately, obesity and polycystic ovary syndrome might share a common genetic predisposition. The cornerstone of managing polycystic ovary syndrome is to address individual symptoms such as hyperandrogenism (hirsutism, acne, and female type boldness), menstrual irregularities, and infertility stemming from anovulation. However, obesity is integral to the pathophysiology of polycystic ovary syndrome and exacerbates all of its features. Therefore, lifestyle modifications aimed at weight reduction should be the primary strategy in overweight or obese women with polycystic ovary syndrome.

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Understanding Adipose Tissue Dysfunction

Matthias BLÜHER

Journal of Obesity & Metabolic Syndrome.2024;33(4):275-288. doi:10.7570/jomes24013

Diseases affecting adipose tissue (AT) function include obesity, lipodystrophy, and lipedema, among others.Both a lack of and excess AT are associated with increased risk for developing diseases including type 2 diabetes mellitus, hypertension, obstructive sleep apnea, and some types of cancer. However, individual risk of developing cardiometabolic and other ‘obesity-related’ diseases is not entirely determined by fat mass. Rather than excess fat accumulation, AT dysfunction may represent the mechanistic link between obesity and comorbid diseases. There are people who remain metabolically healthy despite obesity, whereas people with normal weight or very low subcutaneous AT mass may develop typically obesity-related diseases. AT dysfunction is characterized by adipocyte hypertrophy, impaired subcutaneous AT expandability (ectopic fat deposition), hypoxia, a variety of stress, inflammatory processes, and the release of proinflammatory, diabetogenic, and atherogenic signals. Genetic and environmental factors might contribute to AT heterogeneity either alone or via interaction with intrinsic biological factors. However, many questions remain regarding the mechanisms of AT dysfunction initiation and whether and how it could be reversed. Do AT signatures define clinically relevant subtypes of obesity? Is the cellular composition of AT associated with variation in obesity phenotypes? What roles do environmental compounds play in the manifestation of AT dysfunction? Answers to these and other questions may explain AT disease mechanisms and help to define strategies for improving AT health. This review focuses on recent advances in our understanding of AT biology.

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Weightism in Asia: A Narrative Review and Implications for Practice

Shubashini MATHIALAGAN ; Poh Li LAU

Journal of Obesity & Metabolic Syndrome.2024;33(4):314-325. doi:10.7570/jomes24033

Weightism, also known as weight-related discrimination, is pervasive and believed to be one of the socially accepted types of discrimination in Asia. Weightism is pervasive, impactful, and has significant repercussions on individuals grappling with excess weight. Despite being a major risk factor for obesity, excess weight is not well documented in the Asian literature. This narrative review explores compelling evidence indicating that weightism adversely affects both physical and psychological well-being across various aspects of life. Research findings suggest that weightism be deemed socially unacceptable in Asia to mitigate the obesity epidemic and enhance overall well-being. Consequently, several recommendations for reducing weight stigma in Asian culture are proposed to support a healthier future.

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The Effects of Tirzepatide on Lipid Profile: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

Muhammad Umar MAHAR ; Omar MAHMUD ; Salaar AHMED ; Saleha Ahmed QURESHI ; Wasila Gul KAKAR ; Syeda Sadia FATIMA

Journal of Obesity & Metabolic Syndrome.2024;33(4):348-359. doi:10.7570/jomes24008

Background: Tirzepatide is a novel dual glucose-dependent insulinotropic peptide (GIP)-glucagon-like peptide 1 (GLP-1) receptor agonist being evaluated for the treatment of various metabolic disorders. We performed a meta-analysis of randomized data on the effects of tirzepatide on serum lipid levels. Methods: We systematically searched the PubMed and ClinicalTrials.gov databases for relevant data from randomized controlled clinical trials. All articles were screened, reviewed, and extracted by at least two independent authors, with conflicts resolved by consensus. Four hundred and thirty-three records were identified in the initial literature search; 18 of them were identified for full-text review, and 14 of those were systematically reviewed and included in the analysis. The meta-analysis was performed using an inverse variance random-effects model. Results: Fourteen articles that reported data from 13 randomized controlled clinical trials were included in the review. Nine trials had a low risk of bias, two had a moderate risk, and two had a high risk of bias. The pooled analysis showed that tirzepatide was efficacious at improving all lipid markers, including cholesterol and triglycerides.Moreover, a clear dose response trend was visible across results from groups taking 5, 10, and 15 mg of tirzepatide. Conclusion There is growing evidence to support the use of tirzepatide in patients with metabolic diseases such as type 2 diabetes mellitus, metabolic syndrome, and obesity. Our results demonstrate that tirzepatide significantly improves all aspects of patient metabolism and might be superior in this regard to conventional agents such as insulin formulations or traditional GLP-1 agonists.

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Growth Hormone, Hypothalamic Inflammation, and Aging

Licio A. VELLOSO ; Jose Donato JR.

Journal of Obesity & Metabolic Syndrome.2024;33(4):302-313. doi:10.7570/jomes24032

While inflammation is a crucial response in injury repair and tissue regeneration, chronic inflammation is a prevalent feature in various chronic, non-communicable diseases such as obesity, diabetes, and cancer and in cardiovascular and neurodegenerative diseases. Long-term inflammation considerably affects disease prevalence, quality of life, and longevity. Our research indicates that the growth hormone/insulin-like growth factor 1 (GH/ IGF-1) axis is a pivotal regulator of inflammation in some tissues, including the hypothalamus, which is a key player in systemic metabolism regulation. Moreover, the GH/IGF-1 axis is strongly linked to longevity, as GH- or GH receptor-deficient mice live approximately twice as long as wild-type animals and exhibit protection against aging-induced inflammation. Conversely, GH excess leads to increased neuroinflammation and reduced longevity. Our review studies the associations between the GH/IGF-1 axis, inflammation, and aging, with a particular focus on evidence suggesting that GH receptor signaling directly induces hypothalamic inflammation. This finding underscores the significant impact of changes in the GH axis on metabolism and on the predisposition to chronic, non-communicable diseases.

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Relationships of Thickness of Perirenal Fat with Urinary Levels of MCP-1 and NGAL in Patients with Hypertension

Anna BRAGINA ; Yulia RODIONOVA ; Konstantin OSADCHIY ; Daria BAYUTINA ; Maria K. VASILCHENKO ; Alexander FOMIN ; Valeriy PODZOLKOV

Journal of Obesity & Metabolic Syndrome.2024;33(4):360-366. doi:10.7570/jomes24002

Background: We conducted a study to determine the relationships between perirenal fat (PRF) thickness and urinary levels of monocyte chemoattractant protein-1 (MCP-1) and neutrophil gelatinase-associated lipocalin (NGAL) in patients with hypertension (HTN). Methods: In 338 HTN patients (aged 63.5±12.3 years on average), MCP-1 and NGAL levels were studied using enzyme-linked immunosorbent assay (ELISA). To measure PRF thickness, all patients underwent CT scans. Results: We considered PRF thickness ≥1.91 cm as the diagnostic threshold for perirenal obesity. Patients with excessive PRF thickness exhibited significantly lower levels of MCP-1 and NGAL compared with those with PRF thickness ≥1.91 cm: 0.98 pg/mL (interquartile range [IQR], 0.21 to 2.05) vs. 2.35 pg/mL (IQR, 0.37 to 5.22) for MCP-1 and 50.0 pg/mL (IQR, 48.9 to 67.8) vs. 98.3 pg/mL (IQR, 68.4 to 187.1) for NGAL. We found a relationship of PRF thickness with both MCP-1 (r= 0.46, P<0.05) and NGAL (r= 0.53, P<0.05), the levels of which were significantly different in patients with first- and third-stage chronic kidney disease: 0.33 pg/mL (IQR, 0.21 to 1.35) vs.4.47 pg/mL (IQR, 0.23 to 10.81); 50.0 pg/mL (IQR, 49.4 to 85.5) vs. 126.45 pg/mL (IQR, 57.5 to 205.15), respectively (P=0.04). Patients with metabolically healthy obesity (MHO) had significantly lower MCP-1 levels than those with metabolically unhealthy obesity (MUO): 0.65 pg/mL (IQR, 0.21 to 2.15) vs. 3.28 pg/mL (IQR, 2.05 to 5.22) (P=0.014). MHO patients showed significantly lower NGAL levels than MUO patients: 50.0 pg/mL (IQR, 49.4 to 62.2) vs. 98.3 pg/mL (IQR, 50.0 to 174.8) (P=0.04). Multiple linear regression analysis revealed significant relationships of MCP-1 with PRF thickness (β±standard error, 0.41±0.15; P<0.001) and smoking (0.26±0.13;P= 0.01) and of NGAL with age (0.45±0.16; P<0.01) and PRF thickness (0.49±0.15; P<0.001). Conclusion We identified higher concentrations of renal fibrosis markers in patients with perirenal and MUO as well as a link between PRF thickness and MCP-1 and NGAL levels in urine.

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Association between Body Fat Distribution and Nonalcoholic Fatty Liver Disease/Fibrosis Based on Race/Ethnicity

Donghee KIM ; George CHOLANKERIL ; Aijaz AHMED

Journal of Obesity & Metabolic Syndrome.2024;33(4):326-336. doi:10.7570/jomes24005

Background: Body fat distribution may impact nonalcoholic fatty liver disease (NAFLD) and significant fibrosis differently according to race/ethnicity. We determined the relationship between body fat distribution and NAFLD/ significant fibrosis according to race/ethnicity. Methods: A cross-sectional study of 2,395 participants used the National Health and Nutrition Examination Survey 2017 to 2018. NAFLD and significant fibrosis (≥F2) were defined by controlled attenuation parameter scores and liver stiffness measurements on transient elastography, respectively. Visceral and subcutaneous fat volumes were defined by dual-energy X-ray absorptiometry. Results: The odds ratio (OR) for NAFLD per 1-standard deviation in visceral fat volume and subcutaneous fat volume was 2.05 (95% confidence interval [CI], 1.36 to 3.09) and 1.48 (95% CI, 1.04 to 2.09) in total population, respectively. Visceral fat in non-Hispanic Blacks had the highest odds for NAFLD (OR, 2.86; 95% CI, 1.45 to 5.62), and non-Hispanic Whites (OR, 2.29; 95% CI, 1.19 to 4.40) and non-Hispanic Asians (OR, 1.61; 95% CI, 1.13 to 2.29) were in order. Significant associations between subcutaneous fat volume (OR, 2.10; 95% CI, 1.34 to 3.29; P=0.003) or visceral fat volume (OR, 1.35; 95% CI, 1.05 to 1.73; P=0.023) and significant fibrosis were noted among individuals with NAFLD. Hispanics had the highest odds for NAFLD-associated significant fibrosis (OR, 2.74; 95% CI, 1.32 to 5.70 per 1-standard deviation in subcutaneous fat volume), and non-Hispanic Whites (OR, 2.35; 95% CI, 1.11 to 4.98) and non-Hispanic Asians (OR, 2.01; 95% CI, 1.01 to 4.01) were in order. Conclusion Visceral adiposity was associated with NAFLD and significant fibrosis despite the association of subcutaneous adiposity in NAFLD and significant fibrosis. Racial/ethnic differences in the association between body fat distribution on NAFLD and significant fibrosis were noted.

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Anthropometric Changes in Female Participants Enrolled in a Combined Aerobic and Resistance Training Program for Longer than 1 Year: A Cohort Study

Jung-Sun LIM ; Hee-Jin HWANG ; Yoon Hee EUM ; Ho Jun KIM ; Booyoon CHEUNG ; Han Jin OH ; Bumjo OH

Journal of Obesity & Metabolic Syndrome.2024;33(4):367-373. doi:10.7570/jomes23061

Background: To analyze the anthropometric changes in women who had participated in a combined resistance and aerobic training program for more than a year and to determine the effect of the exercise on weight loss. Methods: A total of 9,128 women aged between 20 and 60 years who registered in the Curves program, which employs a combination of resistance and aerobic training exercises, and who participated for more than 1 year were included in our analysis. The women were divided into groups according to exercise frequency: <1, 1, 2, and ≥3 days/week. Weight and waist circumference were measured at the beginning and end of the follow-up period. Results: The average follow-up duration was 625.3±151.2 days. Waist circumference and body weight decreased more on average in those who participated more frequently in exercise. The achievement of more than 5% weight reduction became more likely with increasing frequency of exercise participation. The odds ratios of more than 5% weight reduction between the exercise groups were 1.47, 1.58, and 2.05 for the 1, 2, and ≥3 days/week exercise groups, respectively. Conclusion Women who participated in a combined resistance and aerobic training program for more than a year lost weight in a dose-dependent manner.

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Predictors of Successful Weight Loss in Extremely Obese Individuals Undergoing Roux-en-Y Gastric Bypass Surgery

Sophia Helena Camargos MOREIRA ; Jacqueline Isaura ALVAREZ-LEITE ; Renan Pedra SOUZA ; Giulia Carregal RESMINI ; Cristina Maria Mendes RESENDE ; Luiz de MARCO ; Luciana BASTOS-RODRIGUES

Journal of Obesity & Metabolic Syndrome.2024;33(4):337-347. doi:10.7570/jomes23067

Background: Roux-en-Y gastric bypass (RYGB) is a standard treatment for severe obesity, but some patients do not achieve the expected success in weight loss. The aim of this study was to evaluate possible predictors of weight loss after RYGB. Methods: Sixty-three patients were included. Pre- and postoperative data were collected from medical records, including comorbidities, anthropometry, energy/macronutrient intake, and physical activity level (PAL). Variants in the brain-derived neurotrophic factor (BDNF; rs6265) and lysophospholipase like 1 (LYPLAL1; rs4846567) genes were investigated. Excess weight loss (EWL) >50% was considered to be successful weight loss (SWL). Logistic regression models were used to verify predictor variables. Results: Participants’ median preoperative body mass index (BMI) was 53 kg/m 2 (interquartile range, 46 to 58).At 12 and 24 months after surgery, EWL was 63% and 67%, and the failure rate was 19% and 16%, respectively.The individuals with insufficient weight loss (IWL) after 12 months had higher preoperative weight, BMI, and overweight. At 24 months, lowest frequency of individuals with SWL in the first year was found in the IWL group.No significant differences were found between the groups in dietary intake and PAL. In the logistic regression, high initial BMI was a predictor of the worst response in both periods, and high initial total weight loss was a predictor of a better response at 24 months. The polymorphism analysis did not show differences between groups in either gene. Conclusion Lower preoperative BMI and greater weight loss at 12 months were predictors of SWL after RYGB.

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Navigating Cardiometabolic Health Behavior during the Pandemic:Strategies for Metabolic Syndrome Management

Junghyun NOH

Journal of Obesity & Metabolic Syndrome.2024;33(2):89-91. doi:10.7570/jomes24024

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