Monocarboxylate transporters: new players in body weight regulation

Carneiro, Lionel; Pellerin, Luc

doi:10.1111/obr.12256

Cited by 40 publications

(55 citation statements)

References 110 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Monocarboxylates that include short-chain fatty acids and ketone bodies have been shown to undergo some alterations during obesity development (4,22,23,43). However, mecha- nisms by which they could be implicated in the pathophysiology of obesity have remained elusive.…”

Section: Discussionmentioning

confidence: 99%

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

Carneiro

Geller

Fioramonti

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

Monocarboxylates have been implicated in the control of energy homeostasis. Among them, the putative role of ketone bodies produced notably during high-fat diet (HFD) has not been thoroughly explored. In this study, we aimed to determine the impact of a specific rise in cerebral ketone bodies on food intake and energy homeostasis regulation. A carotid infusion of ketone bodies was performed on mice to stimulate sensitive brain areas for 6 or 12 h. At each time point, food intake and different markers of energy homeostasis were analyzed to reveal the consequences of cerebral increase in ketone body level detection. First, an increase in food intake appeared over a 12-h period of brain ketone body perfusion. This stimulated food intake was associated with an increased expression of the hypothalamic neuropeptides NPY and AgRP as well as phosphorylated AMPK and is due to ketone bodies sensed by the brain, as blood ketone body levels did not change at that time. In parallel, gluconeogenesis and insulin sensitivity were transiently altered. Indeed, a dysregulation of glucose production and insulin secretion was observed after 6 h of ketone body perfusion, which reversed to normal at 12 h of perfusion. Altogether, these results suggest that an increase in brain ketone body concentration leads to hyperphagia and a transient perturbation of peripheral metabolic homeostasis. energy homeostasis; monocarboxylate transporters; ␤-hydroxybutyrate; obesity; glucose homeostasis DYSFUNCTION IN BOTH CEREBRAL DETECTION OF NUTRIENTS and integration of circulating signals has been implicated in the pathogenesis of obesity and associated disorders (11). For this reason, numerous studies have explored the possible role of nutrient and endocrine sensing of hypothalamic brain areas and their involvement in energy homeostasis regulation (34). The most studied circulating energy substrate is glucose, which represents a critical nutrient monitored by the brain. As the main energy source for brain cells, glucose also plays an important role in brain energy homeostasis (33). However, evidence showing that the brain can use alternative energy substrates has been provided. For instance, fatty acids and ketone bodies contribute significantly to fulfill brain energy needs under specific conditions (6,13,36). Despite the fact that it has been known for decades that cerebral ketone body utilization increases under particular metabolic conditions (13), central ketone body detection has been poorly studied.Under basal conditions, blood ketone body concentrations are low (Ͻ0.3 mmol/l), and their cerebral utilization is considered to be of little significance. However, ketone body levels are increased under conditions such as fasting, type 1 diabetes, or obesity (13). The brain can use ketone bodies when their blood concentrations reach Ϸ4 mmol/l, a value close to the K m of the monocarboxylate transporter 1 (MCT1) expressed on endothelial cells of cerebral blood vessels for ketone bodies (24,31,44). The brain's ability to use ketone bodies varies from...

show abstract

Section: Discussionmentioning

confidence: 99%

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

Carneiro

Geller

Fioramonti

et al. 2016

American Journal of Physiology-Endocrinology and Metabolism

View full text Add to dashboard Cite

show abstract

“…In this respect, they can act as fuel sensors impacting food intake and body weight. Altered MCT expression levels in key tissues in response to metabolic status, especially in the brain, muscles, liver, intestine, pancreas, and adipose tissue are suggested to be important determinants with respect to whole body energy balance 48. As comprehensively reviewed by Carneiro et al ., 48 considerable alterations in MCT1, MCT2, or MCT4 expression in these tissues are found in accordance to metabolic states (e.g., in obese or fasting subjects).…”

Section: Metabolic Diseasesmentioning

confidence: 99%

“…Although, again, most studies refer to rodent or in vitro models, alterations were also confirmed in human tissues. For instance, MCT4 was found to be overexpressed in muscle of obese subjects but decreased after weight loss 48. Most striking results were achieved using a heterozygous transgenic MCT1 knockout mouse model (MCT1 +/− ; MCT1 −/− homozygote knockout is lethal), which has been demonstrated to be resistant to diet‐induced obesity 49.…”

Section: Metabolic Diseasesmentioning

confidence: 99%

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Fisel

Schaeffeler

Schwab

2018

Clinical Translational Sci

View full text Add to dashboard Cite

The solute carrier (SLC) SLC16 gene family comprises 14 members and encodes for monocarboxylate transporters (MCTs), which mediate the absorption and distribution of monocarboxylic compounds across plasma membranes. As the knowledge about their physiological function, activity, and regulation increases, their involvement and contribution to cancer and other diseases become increasingly evident. Moreover, promising opportunities for therapeutic interventions by directly targeting their endogenous functions or by exploiting their ability to deliver drugs to specific organ sites emerge.

show abstract

“…Indeed, several MCT isoforms and their substrates are known to modulate various components of weight homeostasis, ranging from their central effects on food intake to peripheral effects in the browning of white adipose tissue . In reviewing the role of MCTs as new players in weight homeostasis, Carneiro and Pellerin point out that the proof of concept about the potentially critical role of MCT in weight regulation has recently been demonstrated in the ability of haploinsufficient MCT1 mice to resist obesity when exposed to an obesogenic diet – by reducing food intake and intestinal nutrient absorption, as well as increasing resting metabolic rate. Furthermore, they emphasized that the expression of cerebral MCT isoforms can be modulated by alterations of peripheral metabolism and that considering their distribution and their suggested functions in various aspects of metabolism, it is likely that their expression both in the central nervous system and in the periphery might be influenced by nutritional manipulations including caloric restriction and refeeding.…”

Section: Nutrient Transporters: New Players In Weight Regulationmentioning

confidence: 99%

Pathways from dieting to weight regain, to obesity and to the metabolic syndrome: an overview

2015

View full text Add to dashboard Cite

SummaryEvery year, scores of millions of people -as diverse as obese and lean, teenagers and older adults, sedentary and elite athletes, commoners and celebrities -attempt to lose weight on some form of diet. They are often encouraged by their parents, friends, health professionals, training coaches, a media that promotes a slim image and a diet-industry that in Europe and United States alone has an annual turnover in excess of $150 billion. Weight regain is generally the rule, with one-third to two-thirds of the weight lost being regained within 1 year and almost all is regained within 5 years. With studies of the long-term outcomes showing that at least one-third of dieters regain more weight than they lost, together with prospective studies indicating that dieting during childhood and adolescence predicts future weight gain and obesity, there is concern as to whether dieting may paradoxically be promoting exactly the opposite of what it is intended to achieve. Does dieting really make people fatter? How? Does dieting increase the risks for cardiometabolic diseases as many go through repeated cycles of intentional weight loss and unintentional weight regain, i.e. through yo-yo dieting or weight cycling? What's new in adipose tissue biology pertaining to the mechanisms that drive weight regain? Why does exercise not necessarily work in concert with dieting to achieve weight loss and prevent weight regain? What 'lessons' are we learning from bariatric surgery about the mechanisms by which long-term weight loss seems achievable? It is these questions, against a background of preoccupation with dieting, that recent advances and controversies relevant to the theme of 'Pathways from dieting to weight regain, to obesity and to the metabolic syndrome' are addressed in this overview and the eight review articles in this supplement reporting the proceedings of the 7th Fribourg Obesity Research Conference.

show abstract

Monocarboxylate transporters: new players in body weight regulation

Cited by 40 publications

References 110 publications

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

Evidence for hypothalamic ketone body sensing: impact on food intake and peripheral metabolic responses in mice

Clinical and Functional Relevance of the Monocarboxylate Transporter Family in Disease Pathophysiology and Drug Therapy

Pathways from dieting to weight regain, to obesity and to the metabolic syndrome: an overview

Contact Info

Product

Resources

About