Leptin Administration Favors Muscle Mass Accretion by Decreasing FoxO3a and Increasing PGC-1α in ob/ob Mice

Absence of leptin has been associated with reduced skeletal muscle mass in leptin-deficient ob/ob mice. The aim of our study was to examine the effect of leptin on the catabolic and anabolic pathways regulating muscle mass. Gastrocnemius, extensor digitorum longus and soleus muscle mass as well as fiber size were significantly lower in ob/ob mice compared to wild type littermates, being significantly increased by leptin administration (P<0.001). This effect was associated with an inactivation of the muscle atrophy-related transcription factor forkhead box class O3 (FoxO3a) (P<0.05), and with a decrease in the protein expression levels of the E3 ubiquitin-ligases muscle atrophy F-box (MAFbx) (P<0.05) and muscle RING finger 1 (MuRF1) (P<0.05). Moreover, leptin increased (P<0.01) protein expression levels of peroxisome proliferator-activated receptor γ coactivator-1α (PGC-1α), a regulator of muscle fiber type, and decreased (P<0.05) myostatin protein, a negative regulator of muscle growth. Leptin administration also activated (P<0.01) the regulators of cell cycle progression proliferating cell nuclear antigen (PCNA) and cyclin D1, and increased (P<0.01) myofibrillar protein troponin T. The present study provides evidence that leptin treatment may increase muscle mass of ob/ob mice by inhibiting myofibrillar protein degradation as well as enhancing muscle cell proliferation

Vascular targeted nanotherapeutic approach for obesity treatment

Nicole Remaliah Samantha Sibuyi,1 Mervin Meyer,1 Martin Opiyo Onani,2 Amanda Skepu,3 Abram Madimabe Madiehe1 1Department of Science and Technology/Mintek Nanotechnology Innovation Centre, Biolabels Unit, Department of Biotechnology, University of the Western Cape, Bellville, South Africa; 2Organometallics and Nanomaterials, Department of Chemistry, University of the Western Cape, Bellville, South Africa; 3Department of Science and Technology/Mintek Nanotechnology Innovation Centre, Biolabels Unit, Advanced Materials Division, Mintek, Johannesburg, South Africa Abstract: Obesity is a global epidemic that poses a serious health concern due to it being a risk factor for life-threatening chronic diseases, such as type 2 diabetes, cancer, and cardiovascular diseases. Pharmacotherapy remains the mainstay for the management of obesity; however, its usefulness is limited due to poor drug efficacy, non-specificity and toxic side effects. Therefore, novel approaches that could provide insights into obesity and obesity-associated diseases as well as development of novel anti-obesity treatment modalities or improvement on the existing drugs are necessary. While the ideal treatment of obesity should involve early intervention in susceptible individuals, targeted nanotherapy potentially provides a fresh perspective that might be better than the current conventional therapies. Independent studies have shown improved drug efficacy by using prohibitin (PHB)-targeted therapy in obese rodents and non-human primates, thus providing a proof of concept that targeted nanotherapy can be a feasible treatment for obesity. This review presents a brief global survey of obesity, its impact on human health, its current treatment and their limitations, and the role of angiogenesis and PHB in the development of obesity. Finally, the role and potential use of nanotechnology coupled with targeted drug delivery in the treatment of obesity are discussed. Keywords: adipose tissue, angiogenesis, nanomedicine, obesity, prohibitin, targeted drug deliver

CD36 mRNA in the Gastrointestinal Tract Is Differentially Regulated by Dietary Fat Intake in Obesity-Prone and Obesity-Resistant Rats

BACKGROUND: The gastrointestinal tract (GI) is important for detection and transport of consumed nutrients and has been implicated in susceptibility to diet-induced obesity in various rat strains. AIMS: The current studies investigated the regulation of CD36, a receptor which facilitates uptake of long-chain fatty acids, in the GI tract of obesity-prone Osborne–Mendel and obesity-resistant S5B rats fed a high-fat diet. METHODS: Osborne–Mendel and S5B rats consumed a high-fat diet (HFD, 55 % kcal from fat) or a low-fat diet (10 % kcal from fat) for either 3 or 14 days. CD36 messenger RNA (mRNA) levels were measured from circumvallate papillae of the tongue and from duodenal enterocytes. RESULTS: In Osborne–Mendel rats, consumption of HFD for 3 and 14 days led to an increase in CD36 mRNA on circumvallate papillae and in duodenal enterocytes. CD36 mRNA levels were positively correlated with body weight gain and kilocalories consumed at 3 days. In S5B rats, consumption of HFD for 3 days did not alter CD36 mRNA levels on circumvallate papillae or in the duodenum. Duodenal CD36 levels were elevated in S5B rats following 14 days of HFD consumption. CD36 mRNA levels in the duodenum were positively correlated with body weight gain and kilocalories consumed at 14 days. CONCLUSIONS: These data support the differential sensing of nutrients by two regions of the GI tract of obesity-prone and obesity-resistant rats consuming HFD and suggest a role for CD36 in the strain-specific susceptibility to obesity

Early gene response in lithium chloride induced apoptosis

Depending on the cellular context, lithium chloride can lead to enhanced proliferation, cell cycle arrest or apoptosis in mammalian cells. Although substantial work has been made to elucidate the downstream events in the case of lithium chloride-induced cellular proliferation, the molecular response to lithium chloride treatment in the apoptotic scenario is largely undefined. We have used quadruplicate human cDNA arrays with 8000 targets to analyze the early gene response in cultures of human T/C28a cells that undergo apoptosis in response to 20 mM lithium chloride treatment. Incubation of cell cultures with 20 mM lithium chloride for five hours caused alterations in the steady-state mRNA levels of a large number of genes. RT-PCR and real-time RT-PCR confirmed the array results for ten of eleven selected targets. In addition to one protein primarily associated with apoptosis, genes identified as differentially expressed based on microarray data mainly encode proteins involved in basic cellular functions such as signaling, cell cycle control and growth, cell-cell interaction, solute transport and transcription control. We present a list of 50 genes that were differentially expressed in response to lithium chloride treatment and which may represent a reference for further studies to define the pathways governing the apoptotic response to lithium chloride