Drosophilaas a model to study obesity and metabolic disease

Abstract

Excess adipose fat accumulation, or obesity, is a growing problem worldwide in terms of both the rate of incidence and the severity of obesity-associated metabolic disease. Adipose tissue evolved in animals as a specialized dynamic lipid storage depot: adipose cells synthesize fat (a process called lipogenesis) when energy is plentiful and mobilize stored fat (a process called lipolysis) when energy is needed. When a disruption of lipid homeostasis favors increased fat synthesis and storage with little turnover owing to genetic predisposition, overnutrition or sedentary living, complications such as diabetes and cardiovascular disease are more likely to arise. The vinegar fly Drosophila melanogaster (Diptera: Drosophilidae) is used as a model to better understand the mechanisms governing fat metabolism and distribution. Flies offer a wealth of paradigms with which to study the regulation and physiological effects of fat accumulation. Obese flies accumulate triacylglycerols in the fat body, an organ similar to mammalian adipose tissue, which specializes in lipid storage and catabolism. Discoveries in Drosophila have ranged from endocrine hormones that control obesity to subcellular mechanisms that regulate lipogenesis and lipolysis, many of which are evolutionarily conserved. Furthermore, obese flies exhibit pathophysiological complications, including hyperglycemia, reduced longevity and cardiovascular functionsimilar to those observed in obese humans. Here, we review some of the salient features of the fly that enable researchers to study the contributions of feeding, absorption, distribution and the metabolism of lipids to systemic physiology.

High Dietary Sugar Reshapes Sweet Taste to Promote Feeding Behavior in Drosophila melanogaster

“…However, it is unclear whether this reduction is a metabolic consequence of obesity or an effect of diet. To address this question, we fed Drosophila melanogaster fruit flies an established model of a high sugar diet (Musselman et al, 2011; Musselman and Kühnlein, 2018) and assessed their taste responses to sweet stimuli (see STAR Methods for dietary manipulations). Fruit flies fed a 30% sucrose diet for several weeks develop obesity, metabolic syndrome, peripheral insulin resistance, and recapitulate the hallmarks of kidney and heart disease in their corresponding organs (Musselman et al, 2011; Mussel-man and Kühnlein, 2018; Na et al, 2013).…”

“…To address this question, we fed Drosophila melanogaster fruit flies an established model of a high sugar diet (Musselman et al, 2011; Musselman and Kühnlein, 2018) and assessed their taste responses to sweet stimuli (see STAR Methods for dietary manipulations). Fruit flies fed a 30% sucrose diet for several weeks develop obesity, metabolic syndrome, peripheral insulin resistance, and recapitulate the hallmarks of kidney and heart disease in their corresponding organs (Musselman et al, 2011; Mussel-man and Kühnlein, 2018; Na et al, 2013). In contrast, short, up to 1-week exposures to the high sugar diet (SD; 1.4 calories/gram), lead to fat accumulation compared to animals on a control diet (CD; 0.58 calories/gram), (Figures 1A and S1A), but have no effect on Drosophila insulin-like peptide ( dilp ) transcript levels (Figures S2A and S2B).…”

Dietary sugar inhibits satiation by decreasing the central processing of sweet taste

“…3 Like humans and rodents, fruit flies exposed to palatable diets rich in sugar or fat overconsume, gain weight, and become at-risk for obesity and metabolic syndrome (Musselman and Kühnlein 2018) . We recently showed that, in addition to promoting feeding by increasing meal size, consumption of high dietary sugar decreased the electrophysiological and calcium responses of the Gr64f+ sweet sensing neurons to sweet stimuli, independently of weight gain (May et al 2019) .…”

Persistent Epigenetic Reprogramming of Sweet Taste by Diet

“…For all dietary manipulations, the following compounds were mixed into standard cornmeal food (Bloomington Food B recipe) (0.58 calories per gram) by melting, mixing, and pouring new vials as in (Musselman and Kühnlein, 2018) and (Na et al, 2013) . For the 30% sugar diet (1.41 calories per gram) Domino granulated sugar w/v was added.…”