The thrifty lipids: endocannabinoids and the neural control of energy conservation - PubMed (original) (raw)

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The thrifty lipids: endocannabinoids and the neural control of energy conservation

Nicholas V DiPatrizio et al. Trends Neurosci. 2012 Jul.

Abstract

The 'thrifty gene hypothesis' posits that evolution preferentially selects physiological mechanisms that optimize energy storage to increase survival under alternating conditions of abundance and scarcity of food. Recent experiments suggest that endocannabinoids - a class of lipid-derived mediators that activate cannabinoid receptors in many cells of the body - are key agents of energy conservation. The new evidence indicates that these compounds increase energy intake and decrease energy expenditure by controlling the activity of peripheral and central neural pathways involved in the sensing and hedonic processing of sweet and fatty foods, as well as in the storage of their energy content for future use.

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Figures

Figure I

Figure I

Schematic illustrating the main enzymatic steps involved in the formation and hydrolysis of anandamide.

Figure I

Figure I

Schematic representing key central and peripheral organs involved in food intake and energy balance. Gustatory neural signals, including those likely associated with fat or sweet taste, are transmitted from the tongue and oral cavity to the brainstem along the facial (CNVII), glossopharyngeal (CNIX), and vagus (CNX) nerves [22]. These afferent sensory signals terminate in the nucleus of the solitary tract (NST). Neural signals are subsequently transmitted rostrally in rats to the parabrachial nucleus (PBN). Neurons in the NST and PBN respond to and integrate gustatory information derived from the oral cavity, with satiation/satiety-related neural signals transmitted from the gut by the afferent vagus nerve (red arrows). The hindbrain communicates sensory information from food to areas throughout the forebrain, including the nucleus accumbens (NAc) and the hypothalamus (HYP). Importantly, the brain communicates with peripheral organs and tissues, including brown adipose tissue (BAT), liver, white adipose tissue (WAT), and small intestine (SI), via the autonomic nervous system —which comprises vagal afferent and efferents (red arrows), and sympathetics (green arrows) — to maintain food intake and energy balance.

Figure I

Figure I. Endocannabinoid mechanisms are involved in controlling sympathetic activity that drives BAT thermogenesis

(A) Schematic diagram of the rat brain (upper panel) illustrating neural centers in the HYP and BS that control thermogenesis in BAT. Lower panel: Norepinephrine released from sympathetic nerve terminals results in the release of heat from brown adipocytes. (B–C) Electron microscopy revealed increased mitochondrial density in BAT from MGL-transgenic mice (left panel) compared to wild-type mice (right panel). Images adapted from [59]; red asterisk represents mitochondria.

Figure 1

Figure 1

Receptor-dependent production of 2-arachidonoyl-_sn_-glycerol (2-AG) and retrograde signaling at excitatory synapses. The biosynthesis of 2-AG at excitatory synapses may be initiated following spillover of glutamate into the perisynaptic region. Glutamate signaling at type-5 metabotropic glutamate receptors (mGlu5-Rs) stimulates phospholipase C-β (PLC-β) activity generating 1,2-arachidonoylglycerol, which is cleaved by diacylglycerol lipase-α (DGL-α) to produce 2-AG [6, 8, 15]. This endocannabinoid diffuses to the nerve ending where it binds to presynaptic CB1 cannabinoid receptors, reducing both calcium influx at voltage gated calcium channels (VGCC) and vesicular release of glutamate (inhibition denoted by –). 2-AG is rapidly degraded by monoacylglycerol lipase (MGL) and other hydrolases [9] into arachidonic acid (AA) and glycerol.

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References

    1. Neel JV. Diabetes mellitus: a “thrifty” genotype rendered detrimental by “progress”? Am J Hum Genet. 1962;14:353–362. - PMC - PubMed
    1. Matias I, Di Marzo V. Endocannabinoids and the control of energy balance. Trends Endocrinol Metab. 2007;18:27–37. - PubMed
    1. Piomelli D. The molecular logic of endocannabinoid signalling. Nat Rev Neurosci. 2003;4:873–884. - PubMed
    1. Di Marzo V, et al. Formation and inactivation of endogenous cannabinoid anandamide in central neurons. Nature. 1994;372:686–691. - PubMed
    1. Cadas H, et al. Biosynthesis of an endogenous cannabinoid precursor in neurons and its control by calcium and cAMP. J Neurosci. 1996;16:3934–3942. - PMC - PubMed

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