Low glucose induced Alzheimer's disease-like biochemical changes in human induced pluripotent stem cell-derived neurons is due to dysregulated O-GlcNAcylation.

Introduction: Sporadic Alzheimer's disease (sAD) is the leading type of dementia. Brain glucose hypometabolism, along with decreased O-GlcNAcylation levels, occurs before the onset of symptoms and correlates with pathogenesis. Heretofore, the mechanisms involved and the roles of O-GlcNAcylation in sAD pathology largely remain unknown due to a lack of human models of sAD.

Long-chain fatty acyl-CoA synthetase 1 promotes prostate cancer progression by elevation of lipogenesis and fatty acid beta-oxidation.

Fatty acid metabolism is essential for the biogenesis of cellular components and ATP production to sustain proliferation of cancer cells. Long-chain fatty acyl-CoA synthetases (ACSLs), a group of rate-limiting enzymes in fatty acid metabolism, catalyze the bioconversion of exogenous or de novo synthesized fatty acids to their corresponding fatty acyl-CoAs. In this study, systematical analysis of ACSLs levels and the amount of fatty acyl-CoAs illustrated that ACSL1 were significantly associated with the levels of a broad spectrum of fatty acyl-CoAs, and were elevated in human prostate tumors.

Generation of Functional Brown Adipocytes from Human Pluripotent Stem Cells via Progression through a Paraxial Mesoderm State.

Brown adipocytes (BAs) are a potential cell source for the treatment of metabolic disease, including type 2 diabetes. In this report, human pluripotent stem cells (hPSCs) are subject to directed differentiation through a paraxial mesoderm progenitor state that generates BAs at high efficiency. Molecular analysis identifies potential regulatory networks for BA development, giving insight into development along this lineage.

Human beige adipocytes for drug discovery and cell therapy in metabolic diseases.

Human beige adipocytes (BAs) have potential utility for the development of therapeutics to treat diabetes and obesity-associated diseases. Although several reports have described the generation of beige adipocytes in vitro, their potential utility in cell therapy and drug discovery has not been reported. Here, we describe the generation of BAs from human adipose-derived stem/stromal cells (ADSCs) in serum-free medium with efficiencies >90%.

Mitochondrial-specific autophagy linked to mitochondrial dysfunction following traumatic freeze injury in mice.

The objective of this study was to interrogate the link between mitochondrial dysfunction and mitochondrial-specific autophagy in skeletal muscle. C57BL/6J mice were used to establish a time course of mitochondrial function and autophagy induction after fatigue ( = 12), eccentric contraction-induced injury ( = 20), or traumatic freeze injury (FI, = 28); only FI resulted in a combination of mitochondrial dysfunction, i.e.

NaCl Nanoparticles as a Cancer Therapeutic.

Many inorganic nanoparticles are prepared and their behaviors in living systems are investigated. Yet, common electrolytes such as NaCl are left out of this campaign. The underlying assumption is that electrolyte nanoparticles will quickly dissolve in water and behave similarly as their constituent salts.

Ectopic brown adipose tissue formation within skeletal muscle after brown adipose progenitor cell transplant augments energy expenditure.

Brown adipose tissue (BAT) thermogenesis increases energy expenditure (EE). Expanding the volume of active BAT transplantation holds promise as a therapeutic strategy for morbid obesity and diabetes. Brown adipose progenitor cells (BAPCs) can be isolated and expanded to generate autologous brown adipocyte implants.

Dietary palmitate cooperates with Src kinase to promote prostate tumor progression.

Numerous genetic alterations have been identified during prostate cancer progression. The influence of environmental factors, particularly the diet, on the acceleration of tumor progression is largely unknown. Expression levels and/or activity of Src kinase are highly elevated in numerous cancers including advanced stages of prostate cancer.

PGC-1α overexpression partially rescues impaired oxidative and contractile pathophysiology following volumetric muscle loss injury.

Volumetric muscle loss (VML) injury is characterized by a non-recoverable loss of muscle fibers due to ablative surgery or severe orthopaedic trauma, that results in chronic functional impairments of the soft tissue. Currently, the effects of VML on the oxidative capacity and adaptability of the remaining injured muscle are unclear. A better understanding of this pathophysiology could significantly shape how VML-injured patients and clinicians approach regenerative medicine and rehabilitation following injury.

Fat spectral modeling on triglyceride composition quantification using chemical shift encoded magnetic resonance imaging.

Purpose: To explore, at a high field strength of 7T, the performance of various fat spectral models on the quantification of triglyceride composition and proton density fat fraction (PDFF) using chemical-shift encoded MRI (CSE-MRI).

Methods: MR data was acquired from CSE-MRI experiments for various fatty materials, including oil and butter samples and in vivo brown and white adipose mouse tissues. Triglyceride composition and PDFF were estimated using various a priori 6- or 9-peak fat spectral models.

Response gene to complement 32 suppresses adipose tissue thermogenic genes through inhibiting β3-adrenergic receptor/mTORC1 signaling.

Our previous studies have shown that response gene to complement (RGC)-32 deficiency (Rgc32) protects mice from diet-induced obesity and increases thermogenic gene expression in adipose tissues. However, the underlying mechanisms by which RGC-32 regulates thermogenic gene expression remain to be determined. In the present study, RGC-32 expression in white adipose tissue (WAT) was suppressed during cold exposure-induced WAT browning.

Transient HIF2A inhibition promotes satellite cell proliferation and muscle regeneration.

The remarkable regeneration capability of skeletal muscle depends on the coordinated proliferation and differentiation of satellite cells (SCs). The self-renewal of SCs is critical for long-term maintenance of muscle regeneration potential. Hypoxia profoundly affects the proliferation, differentiation, and self-renewal of cultured myoblasts.

MYC Controls Human Pluripotent Stem Cell Fate Decisions through Regulation of Metabolic Flux.

As human pluripotent stem cells (hPSCs) exit pluripotency, they are thought to switch from a glycolytic mode of energy generation to one more dependent on oxidative phosphorylation. Here we show that, although metabolic switching occurs during early mesoderm and endoderm differentiation, high glycolytic flux is maintained and, in fact, essential during early ectoderm specification. The elevated glycolysis observed in hPSCs requires elevated MYC/MYCN activity.

DOCK2 deficiency mitigates HFD-induced obesity by reducing adipose tissue inflammation and increasing energy expenditure.

Obesity is the major risk factor for type 2 diabetes, cardiovascular disorders, and many other diseases. Adipose tissue inflammation is frequently associated with obesity and contributes to the morbidity and mortality. Dedicator of cytokinesis 2 (DOCK2) is involved in several inflammatory diseases, but its role in obesity remains unknown.

Isoproterenol Increases Uncoupling, Glycolysis, and Markers of Beiging in Mature 3T3-L1 Adipocytes.

Beta-adrenergic activation stimulates uncoupling protein 1 (UCP1), enhancing metabolic rate. In vitro, most work has studied brown adipocytes, however, few have investigated more established adipocyte lines such as the murine 3T3-L1 line. To assess the effect of beta-adrenergic activation, mature 3T3-L1s were treated for 6 or 48 hours with or without isoproterenol (10 and 100 μM) following standard differentiation supplemented with thyroid hormone (T3; 1 nM).