Maternal Metformin Intervention during Obese Glucose-Intolerant Pregnancy Affects Adiposity in Young Adult Mouse Offspring in a Sex-Specific Manner

Background: Metformin is commonly used to treat gestational diabetes mellitus. This study investigated the effect of maternal metformin intervention during obese glucose-intolerant pregnancy on the gonadal white adipose tissue (WAT) of 8-week-old male and female mouse offspring. Methods: C57BL/6J female mice were provided with a control (Con) or obesogenic diet (Ob) to induce pre-conception obesity. Half the obese dams were treated orally with 300 mg/kg/d of metformin (Ob-Met) during pregnancy. Gonadal WAT depots from 8-week-old offspring were investigated for adipocyte size, macrophage infiltration and mRNA expression of pro-inflammatory genes using RT-PCR. Results: Gestational metformin attenuated the adiposity in obese dams and increased the gestation length without correcting the offspring in utero growth restriction and catch-up growth caused by maternal obesity. Despite similar body weight, the Ob and Ob-Met offspring of both sexes showed adipocyte hypertrophy in young adulthood. Male Ob-Met offspring had increased WAT depot weight (p < 0.05), exaggerated adipocyte hyperplasia (p < 0.05 vs. Con and Ob offspring), increased macrophage infiltration measured via histology (p < 0.05) and the mRNA expression of F4/80 (p < 0.05). These changes were not observed in female Ob-Met offspring. Conclusions: Maternal metformin intervention during obese pregnancy causes excessive adiposity, adipocyte hyperplasia and WAT inflammation in male offspring, highlighting sex-specific effects of prenatal metformin exposure on offspring WAT.

Long Noncoding RNAs: Novel Important Players in Adipocyte Lipid Metabolism and Derivative Diseases

Obesity, a global public health issue, is characterized by excessive adiposity and is strongly related to some chronic diseases including cardiovascular diseases and diabetes. Extra energy intake-induced adipogenesis involves various transcription factors and long noncoding RNAs (lncRNAs) that control lipogenic mRNA expression. Currently, lncRNAs draw much attention for their contribution to adipogenesis and adipose tissue function. Increasing evidence also manifests the pivotal role of lncRNAs in modulating white, brown, and beige adipose tissue development and affecting the progression of the diseases induced by adipose dysfunction. The aim of this review is to summarize the roles of lncRNAs in adipose tissue development and obesity-caused diseases to provide novel drug targets for the treatment of obesity and metabolic diseases.

PSV-28 Feeding Ractopamine Improves Growth Performance and Carcass Characteristics of the Lard-type Mangalica Pig

Mangalica pigs are a popular niche breed given their reputation for superior quality pork; however, the slow growth rate, poor lean yield and excessive adiposity exhibited by this breed limits its widespread adoption. Our objective was to determine if feeding Ractopamine (RAC), a metabolic modifier that improves feed efficiency and lean yield, would improve growth performance without impairing pork quality in the Mangalica. To accomplish this, a growth trial was conducted whereby pigs (n = 28) weighing 73 kg were fed a standard grower ration supplemented with either 0 or 22 ppm RAC for 21 days during which daily feed intakes and weekly body weights were recorded for all animals. Then pigs were finished to a 105 kg harvest weight. At 24h postmortem, carcasses were ribbed at the 10th rib to facilitate pork quality and carcass composition measurements. Primal cuts were fabricated and individually weighed. As hypothesized, RAC increased ADG (P &lt; 0.04) and feed efficiency (P &lt; 0.03) 24% and 21% respectively. However, unexpectedly, RAC failed to suppress voluntary feed intake (P &gt; 0.71). Interestingly RAC increased LEA (P &lt; 0.0001) by 21% but did not impact 10th rib fat depth (P &gt; 0.90) or marbling score (P &gt; 0.77). Likewise, RAC failed to alter any primal cut weights. Feeding RAC lowered b* values (P &lt; 0.04) and tended to lower L* values (P &lt; 0.08) while not affecting a* values (P &gt; 0.30) suggesting RAC darkened loin color. Finally, RAC improved cook loss percentage (P &lt; 0.02) 11% while not impacting WBSF (P &gt; 0.31). Collectively, these data support the hypothesis that feeding RAC to the lard type Mangalica pig improves growth performance without impairing pork quality in this breed. Feeding RAC may be a viable strategy to improve the economic feasibility of utilizing this breed to target niche markets.

Reconnoitering the role of Endothelin in Obesity

Background:: Obesity, metabolic disorders and diabetes mellitus are allied with increased cardiovascular risk. Given the vasoconstrictor activity of endothelin, enhanced endothelin has been hypothesized to take part in the disorder of adiposity associated vascular homeostasis. Moreover, elevated endothelin subsidizes endothelin dysregulated related to obesity, diabetes mellitus whereas alleviating the endothelin vasoconstrictor tone amends the unreliable endothelium - dependent vasodilation. Objective: The main objective of the current manuscript is to enumerate the intrinsic role of endothelin in obesity and related complications. Methods: A deep research on the literature available till date for endothelin in obesity as conducted using various medical sites like PubMed, MEDLINE from internet and data was collected. The articles were majorly preferred in English language. Results: The substantial effect of obesity on the progression of cardiac disorders has generated persistent efforts to expose the action associating with excessive adiposity to vascular dysregulation. Reduced vasodilator activity has been predicted as an early hemodynamic defect in obese individuals, also elevated vasoconstrictor tone elicits to vascular impairment. In certain, upregulation of endothelin activity, constantly reported in obese subjects, hasten obesity and its related complication, specifying the inflammatory and mitogenic activities of endothelin. Recently, various gut hormones, in association with their role as an accent of food intake, energy homeostasis, and triglycerides metabolism have reported numerous vascular properties. They escalate the bioavailability of vasodilators mediator i.e. nitric oxide and prevent the endothelin activity. These characteristics make gut hormones a favorable approach for targeting both metabolic and cardiovascular conditions of obesity. Conclusion: The present review demonstrates the intrinsic role of endothelin as a novel molecule in the progression of obesity and focuses on the status of endothelin inhibitors as a therapeutic potential in preventing obesity and related complications.

Menopausal Transition, Body Mass Index, and Prevalence of Mammographic Dense Breasts in Middle-Aged Women

The interrelationship between menopausal stage, excessive adiposity and dense breasts remains unclear. We aimed to investigate the relationship between menopausal stage and dense-breast prevalence in midlife women while considering a possible effect modification of being overweight. The present cross-sectional study comprised 82,677 Korean women, aged 35–65 years, who attended a screening exam. Menopausal stages were categorized based on the Stages of Reproductive Aging Workshop (STRAW + 10) criteria. Mammographic breast density was categorized according to Breast Imaging Reporting and Data System (BI-RADS). Dense breasts were defined as BI-RADS Breast Density category D (extremely dense). The prevalence of dense breasts decreased as menopausal stage increased (p-trend < 0.001), and this pattern was pronounced in overweight women than non-overweight women (p-interaction = 0.016). Compared with pre-menopause, the multivariable-adjusted prevalence ratios (and 95% confidence intervals) for dense breasts were 0.98 (0.96–1.00) in early transition, 0.89 (0.86–0.92) in late transition, and 0.55 (0.52–0.59) in post-menopause, among non-overweight women, while corresponding prevalence ratios were 0.92 (0.87–0.98), 0.83 (0.77–0.90) and 0.36 (0.31–0.41) among overweight women. The prevalence of dense breasts was inversely associated with increasing menopausal stages and significantly decreased from the late menopausal transition, with stronger declines among overweight women.

Excessive adiposity is associated with an inflammation induced elevation in serum hepcidin, serum ferritin and increased risk of iron overload

Excess body fat is associated with the production of pro-inflammatory molecules from dysfunctional adipose tissue resulting in systemic inflammation. Inflammation stimulates expression of the iron regulatory hormone hepcidin, resulting in elevated serum ferritin and iron overload in metabolic tissues. Hepcidin driven iron maldistribution may be implicated in the development of metabolic diseases such as Type 2 diabetes and CVD. The aim of this study was to investigate the effect of body fat and the associated inflammation on markers of iron homeostasis.Analyses were based on data from the cross-sectional National Adult Nutrition Survey (2008–2010) (www.iuna.net). Percentage body fat (BF%) of participants (n = 1211) was measured by a Tanita BC420MA device. Participants were classified as healthy, overweight or obese based on age and gender-specific BF% ranges. Serum ferritin and serum hepcidin were measured using immunoturbidimetric immunoassays. ANCOVA with Bonferroni post hoc (p < 0.05) was used to compare anthropometric parameters, biochemical markers of iron status and inflammation and nutrient intakes between BF% groups. Predictors of serum hepcidin and serum ferritin were determined using linear regression analysis.In the population 42% were classified as healthy, 33% as overfat and 25% as obese. Serum hepcidin was significantly elevated in obese participants (8.42ng/ml ± 4.2) compared to their healthy counterparts (6.49ng/ml ± 3.9)(p < 0.001). Significantly higher serum ferritin was observed in obese (223ng/ml ± 170) and overfat males (166ng/ml ± 120) compared to healthy males (135ng/ml ± 91)(p < 0.001). A significant percentage of overweight (20%) and obese (32%) participants were at severe risk of iron overload compared to healthy participants (8%)(p < 0.001). No significant differences in dietary iron intakes were observed between BF% groups. Linear regression analysis indicated that BF% was a significant (p < 0.001) predictor of hepcidin in males (β = 0.327) and females (β = 0.226). IL-6 (β = 0.317,p < 0.001) and TNFα (β = 0.229,p < 0.001) were the strongest inflammatory predictors of hepcidin in females only. In males, leptin was a positive predictor (β = 0.159,p = 0.003) of hepcidin, while adiponectin displayed a negative predictive relationship (β = -0.145,p = 0.001)Our results indicate that excessive adiposity is associated with elevated serum ferritin and hepcidin independent of dietary intake. Cytokines are a potential driver of hepcidin in females, with adipose-derived hormones seeming to have the greater effect in males. These results may help to elucidate the relationship between obesity and dysregulated iron metabolism. Further research is required to investigate the metabolic effects of hepcidin-induced iron overload in those with excess body fat.

Role of Obesogens in the Pathogenesis of Obesity

Obesity is considered to be a 20th century pandemic, and its prevalence correlates with the increasing global pollution and the presence of chemical compounds in the environment. Excessive adiposity results from an imbalance between energy intake and expenditure, but it is not merely an effect of overeating and lack of physical activity. Recently, several compounds that alter the mechanisms responsible for energy homeostasis have been identified and called “obesogens”. This work presents the role of obesogens in the pathogenesis of obesity. We reviewed data from in vitro animal and human studies concerning the role of obesogens in the disturbance of energy homeostasis. We identified (i) the main groups and classes of obesogens, (ii) the molecular mechanisms of their action, (iii) their deleterious effect on adipose tissue function and control of appetite, and (iv) possible directions in limiting their influence on human metabolism. Obesogens have a multifactorial detrimental influence on energy homeostasis. Focusing on limiting exposure to obesogens and improving early life nutrition seems to be the most reasonable direction of action to prevent obesity in future generations.

Obesity-induced immune dysfunction and immunosuppression: TEM observation of visceral and subcutaneous lymph node microarchitecture and immune cell interactions

BackgroundInflammation, induced by excessive adiposity, links obesity to disease risk yet little attention has been devoted to the lymphoid tissues embedded within adipose tissue depots. Lymph nodes are the primary site for the development of protective immunity, hence any disease process that affects these tissues will also directly impact immunity. Here we examined how obesity alters secondary lymphatic tissue structure and encapsulated immune cells.Materials and methodsFour-month-old C57BL/6 male mice were fed standard rodent chow or a Western high fat diet (HFD) for 6 months. Center regions of visceral and subcutaneous lymph nodes (SQLNS) were observed via transmission electron microscopy (TEM).ResultsCompared with chow, HFD-induced obesity deleteriously modified the structural microarchitecture and immune cell morphology of visceral and SQLNs. In HFD mice, fibroblastic reticular cells (FRCs) were dysregulated while laying among excessive amounts of disorganized collagen (C). In addition HFD lymph nodes contained a disproportionate amount of cellular debris from damaged or dead cells, increased sinus spacing and decreased immune cell interactions. Specifically, dendritic cells (DCs) that are necessary for adaptive immune response where embedded among extracellular debris with decreased pseudopodia. Similarly, the extraneous fibrous extracellular matrix (ECM) in HFD mice limited contact between lymphocytes (LCs) causing their microvilli extensions to decrease.DiscussionOverall, excessive C production within lymph nodes, driven by diet-induced obesity, creates a physical barrier that impedes proper lymph flow and cellular communication. Obesity-induced disorganization of the immune cell guidance network interrupts immune cell adhesion and consequently inhibits travel within cortex regions needed for cell interactions, survival and proliferation.