Heritable changes in chromatin contacts linked to transgenerational obesity.

Burgeoning evidence demonstrates that effects of environmental exposures can be transmitted to subsequent generations through the germline without DNA mutations. This phenomenon remains controversial because underlying mechanisms have not been identified. Therefore, understanding how effects of environmental exposures are transmitted to unexposed generations without DNA mutations is a fundamental unanswered question in biology.

Palmitoleic acid ameliorates palmitic acid-induced proinflammation in J774A.1 macrophages via TLR4-dependent and TNF-α-independent signallings.

Adipose tissue resident macrophages play an important role in the regulation of the inflammatory response. Monounsaturated fatty acids assist in the prevention of cardiovascular diseases via an anti-inflammatory effect. However, the mechanisms by which monounsaturated fatty acids, such as palmitoleic acid, regulate the inflammatory response has not been well investigated.

Disconnect between alcohol-induced alterations in chromatin structure and gene transcription in a mouse embryonic stem cell model of exposure.

Alterations to chromatin structure induced by environmental insults have become an attractive explanation for the persistence of exposure effects into subsequent life stages. However, a growing body of work examining the epigenetic impact that alcohol and other drugs of abuse exert consistently notes a disconnection between induced changes in chromatin structure and patterns of gene transcription. Thus, an important question is whether perturbations in the 'histone code' induced by prenatal exposures to alcohol implicitly subvert gene expression, or whether the hierarchy of cellular signaling networks driving development is such that they retain control over the transcriptional program.

The Effects of Metformin on Obesity-Induced Dysfunctional Retinas.

Purpose: The purpose of this study was to determine the effects of metformin on dysfunctional retinas in obesity-induced type 2 diabetic mice.

Methods: A high-fat diet (HFD)-induced diabetic mouse model (C57BL/6J) was used in this study. After 2 months of the HFD regimen, HFD mice were given daily metformin through oral gavage.

Deletion of miR-150 Exacerbates Retinal Vascular Overgrowth in High-Fat-Diet Induced Diabetic Mice.

Diabetic retinopathy (DR) is the leading cause of blindness among American adults above 40 years old. The vascular complication in DR is a major cause of visual impairment, making finding therapeutic targets to block pathological angiogenesis a primary goal for developing DR treatments. MicroRNAs (miRs) have been proposed as diagnostic biomarkers and potential therapeutic targets for various ocular diseases including DR.

miR-150 regulates obesity-associated insulin resistance by controlling B cell functions.

Adipose tissue resident B cells account for more than 20% of stromal cells within visceral adipose tissues; however, their functions in the adipose tissue niche are poorly elucidated. Here we report that miR-150 modulates adipose tissue function by controlling activation of B cells and their interactions with other immune cells. miR-150KO mice displayed exacerbated obesity-associated tissue inflammation and systemic insulin resistance, which is recapitulated by adoptive transfer of B cells, but not purified immunoglobulin, into obese B(null) mice.

MicroRNA-223 is a crucial mediator of PPARγ-regulated alternative macrophage activation.

Polarized activation of adipose tissue macrophages (ATMs) is crucial for maintaining adipose tissue function and mediating obesity-associated cardiovascular risk and metabolic abnormalities; however, the regulatory network of this key process is not well defined. Here, we identified a PPARγ/microRNA-223 (miR-223) regulatory axis that controls macrophage polarization by targeting distinct downstream genes to shift the cellular response to various stimuli. In BM-derived macrophages, PPARγ directly enhanced miR-223 expression upon exposure to Th2 stimuli.

High-Fat Diet-Induced Retinal Dysfunction.

Purpose: The purpose of this study was to investigate the impact of obesity-induced prediabetes/early diabetes on the retina to provide new evidence on the pathogenesis of type 2 diabetes-associated diabetic retinopathy (DR).

Methods: A high-fat diet (HFD)-induced obesity mouse model (male C57BL/6J) was used in this study. At the end of the 12-week HFD feeding regimen, mice were evaluated for glucose and insulin tolerance, and retinal light responses were recorded by electroretinogram (ERG).

MicroRNAs Control Macrophage Formation and Activation: The Inflammatory Link between Obesity and Cardiovascular Diseases.

Activation and recruitment of resident macrophages in tissues in response to physiological stress are crucial regulatory processes in promoting the development of obesity-associated metabolic disorders and cardiovascular diseases. Recent studies have provided compelling evidence that microRNAs play important roles in modulating monocyte formation, macrophage maturation, infiltration into tissues and activation. Macrophage-dependent systemic physiological and tissue-specific responses also involve cell-cell interactions between macrophages and host tissue niche cell components, including other tissue-resident immune cell lineages, adipocytes, vascular smooth muscle and others.