Biology subjects

Megha, M.

Publications and source records attributed to Megha, M..

3 recordsLinked to original sources

bioRxiv2024

Dietary Phyllanthus emblica L. (Indian gooseberry, Amla) improves fecundity and resistance to oxidative stress in a Drosophila melanogaster model of early-life malnutrition.

Amla is a celebrated ethnobotanical fruit whose consumption is associated with several beneficial claims. Many studies have demonstrated Amlas positive impact on molecular and systemic readouts in diseased conditions. Studies on Amlas potential as a nutraceutical however are limited. To test if daily dietary supplementation with Amla improves select systemic readouts associated with wellbeing, and alleviate phenotypes associated with early life malnutrition, we deployed the fly animal model system. Benefits were compared between adult flies that were subject to larval starvation (ELS) and controls, and between genders. The most dramatic effect was observed in resistance to oxidative stress: prophylactic feeding of 1% Amla Juice (AJ) increased median survival by [~]75% (control) and 200% (ELS) in males, and [~]167% (control) and [~]150% (ELS) in females, respectively. Interestingly, survival also increased in both genders when AJ was fed only during stress or, before and during stress. For other assays, impacts were seen only in ELS flies: AJ feeding decreased lifespan in female ELS flies, increased egg numbers by [~]25% and improved survival upon P. entomophila infection by [~]80%. Together, these suggest that prophylactic AJ dietary intake has selective biological effects and in the context of malnutrition, it can be explored further as a nutraceutical. O_FIG O_LINKSMALLFIG WIDTH=200 HEIGHT=108 SRC="FIGDIR/small/626288v1_ufig1.gif" ALT="Figure 1"> View larger version (25K): org.highwire.dtl.DTLVardef@d66901org.highwire.dtl.DTLVardef@87e4fcorg.highwire.dtl.DTLVardef@1ca7027org.highwire.dtl.DTLVardef@18922cc_HPS_FORMAT_FIGEXP M_FIG C_FIG

developmental biology↗

bioRxiv2024

Green Jackfruit Flour Prevents Metabolic Dysfunction-Associated Steatohepatitis and Progression to Hepatocellular Carcinoma via the AMPK and MAPK Signaling Pathways

Metabolic dysfunction-associated steatotic liver disease (MASLD), encompassing metabolic-dysfunction associated steatotic liver (MAFL) and steatohepatitis (MASH), which further progresses to hepatocellular carcinoma (HCC), is a serious public health concern. Given the paucity of approved therapeutic strategies for this lifestyle disorder, dietary interventions may prove effective. We evaluated how green jackfruit flour (JF) prevents MASH and progression to HCC and its underlying mechanisms. The study utilized two murine models that mimicked human MASLD disease: (i) a diet-induced MASH model; (ii) a MASH-HCC model induced by diet and a very low dose of CCl4. C57Bl/6 mice were fed with chow (CD) or western diet (WD) with normal (NW) or sugar water (SW) for 12 weeks, then randomized to receive either 5 kcal% green jackfruit flour (JF) or an equal volume of placebo flour (PB). The biochemical, histological, and molecular analyses were assessed. JF significantly reduced body weight, liver injury, insulin resistance, and alleviated obesity, steatosis, inflammation, fibrosis, and tumor development in WDSW or WDSW/CCl4 mice compared to placebo groups. Furthermore, JF activated AMPK (AMP-activated protein kinase) and inhibited MAPK (mitogen-activated protein kinase) signaling pathways in MASH and MASH-HCC experimental models, respectively. This was supported by sodium propionate treatment, the primary short-chain fatty acid entering the liver from JFs soluble fiber microbial fermentation, which also regulated AMPK and MAPK signaling in cellular models of MASH and HCC, respectively. Hence, our findings present strong evidence of JFs therapeutic potential in the prevention of MASH and MASH-HCC, warranting further investigation of JFs efficacy as a dietary intervention in clinical trials.

cancer biology↗

bioRxiv2022

Impact of late larval nutritional stress on adult metabolic, gut and locomotor phenotypes in Drosophila melanogaster

Dietary quantity and quality are key determinants for insect development from egg to adult. When nutritional deficiency is sub-optimal, development is completed, albeit resulting in an adult insect that is smaller than normal in size. If now fed a normal diet, would the smaller adults be similar to normally developed flies? To begin to answer this question, we characterised a few physiological and musculoskeletal readouts. Larvae were subject to acute starvation in late stages of development, and the resulting adults (Early Life Starved; ELS) maintained on a normal diet, were tested for biochemistry, gut physiology and locomotor activity. In females, no significant difference was observed in biochemical readouts for the whole-body or hemolymph, between control and ELS flies. In males, whole-body glucose and hemolymph trehalose were significantly reduced in ELS flies. Interestingly, ELS flies of both sexes respond with a disproportionally higher accumulation of triacylglycerides (TAGs) when on a high-fat diet. Age-related changes in the adult gut were compared between control and ELS flies: these revealed an increased proportion of ELS flies with loss of gut barrier integrity, deviant number of intestinal stem cells and no difference in enteroendocrine cells. The rate of antimicrobial peptide gene expression to an enteric infection challenge was also slower in ELS flies. For musculoskeletal readouts, climbing and flight behaviour were measured. In population assays, both male and female ELS flies showed climbing deficits. In a fine-scale climbing assay on individual flies, female but not male ELS flies showed higher climbing speed, while males but not females, showed lower geotactic index. This collection of phenotypic assessments show that firstly, larval undernutrition, even when not lethal, continues to impact adult functioning. Secondly, for some phenotypes, a normal diet in adults exposed to early life malnutrition is insufficient to restore optimal functioning. Thirdly, larval dietary loss affects adult insects in a sex-dependent manner. This study lays the framework to uncover the molecular, cellular and hormonal mechanisms that are altered by early life malnutrition. Furthermore, these readouts may be used to develop Drosophila as a high-throughput model for interrogating the efficacy of diet therapies to address malnutrition.

developmental biology↗