Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice

Varady, Kristina A.; Roohk, Donald J.; Loe, Yu-chi Cynthia; McEvoy-Hein, B. K.; Hellerstein, Marc K.

doi:10.1194/jlr.m700223-jlr200

Cited by 75 publications

(70 citation statements)

References 29 publications

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“…A similar phenomenon is observed during caloric restriction and intermittent fasting, both of which are associated with improved systemic insulin sensitivity. 36 For instance, Varady et al 37 show that intermittent fasting induces increased lipolysis, increased lipogenesis, decreased adipocyte size, but no change in total fat mass. Furthermore, the concept of metabolic flexibility (or loss thereof) in muscle in the context of type 2 diabetes has found widespread acceptance through the elegant work of Kelley.…”

Section: Discussionmentioning

confidence: 99%

Enhanced Metabolic Flexibility Associated with Elevated Adiponectin Levels

Asterholm

Scherer

2010

The American Journal of Pathology

140

122

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Metabolically healthy individuals effectively adapt to changes in nutritional state. Here , we focus on the effects of the adipocyte-derived secretory molecule adiponectin on adipose tissue in mouse models with genetically altered adiponectin levels. We found that higher adiponectin levels increased sensitivity to the lipolytic effects of adrenergic receptor agonists. In parallel , adiponectin-overexpressing mice also display enhanced clearance of circulating fatty acids and increased expansion of subcutaneous adipose tissue with chronic high fat diet (HFD) feeding. These adaptive changes to the HFD were associated with increased mitochondrial density in adipocytes , smaller adipocyte size , and a general transcriptional up-regulation of factors involved in lipid storage through efficient esterification of free fatty acids. The physiological response to adiponectin overexpression resembles in many ways the effects of chronic exposure to ␤ 3 -adrenergic agonist treatment , which also results in improvements in insulin sensitivity. In addition, using a novel computed tomography-based method for measurements of hepatic lipids , we resolved the temporal events taking place in the liver in response to acute HFD exposure in both wild-type and adiponectin-overexpressing mice. Increased levels of adiponectin potently protect against HFD-induced hepatic lipid accumulation and preserve insulin sensitivity. Given these profound effects of adiponectin, we propose that adiponectin is a factor that increases the metabolic flexibility of adipose tissue, enhancing its ability to maintain proper function under metabolically challenging conditions. (Am J Pathol

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Section: Discussionmentioning

confidence: 99%

Enhanced Metabolic Flexibility Associated with Elevated Adiponectin Levels

Asterholm

Scherer

2010

The American Journal of Pathology

140

122

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“…Different variants of intermittent energy restriction (CR for intermittent periods of time) have been reported to have health‐promoting effects. These beneficial health effects include improvements of body composition 12, 13, 14, skin wound healing 9, blood pressure and cardiovascular health markers 15, 16, neurological health and cognitive performance 17, 18, 19 and retarded tumor growth/formation 20, 21, 22, 23. By applying repetitive cycles of fasting/CR and regular eating, the negative side effects of CR are thought to be circumvented.…”

Section: Introductionmentioning

confidence: 99%

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Lute

Boekschoten

Dijk

et al. 2017

Molecular Nutrition Food Res

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ScopeCalorie restriction (CR) has been shown to extend life‐ and health‐span in model species. For most humans, a life‐long CR diet is too arduous to adhere to. The aim of this study was to explore whether weekly intermittent CR can (1) provide long‐term beneficial effects and (2) counteract diet‐induced obesity in male aging mice.Methods and resultsIn this study, we have exposed C57Bl/6J mice for 24 months to an intermittent (INT) diet, alternating weekly between CR of a control diet and ad libitum moderate‐fat (MF) feeding. This weekly intermittent CR significantly counteracted the adverse effects of the MF diet on mortality, body weight, and liver health markers in 24‐month‐old male mice. Hepatic gene expression profiles of INT‐exposed animals appeared much more comparable to CR‐ than to MF‐exposed mice. At 12 months of age, a subgroup of MF‐exposed mice was transferred to the INT diet. Gene expression profiles in the liver of the 24‐month‐old diet switch mice were highly similar to the INT‐exposed mice. However, a small subset of genes was consistently changed by the MF diet during the first phase of life.ConclusionWeekly intermittent CR largely, but not completely, reversed adverse effects caused by a MF diet.

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“…The majority of rodent studies (6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17)(18)(19)(20)(21) and a small number of human studies (22)(23)(24)(25)(26) have used IER protocols, which completely restrict energy intake (i.e. 100 % energy restriction) every other day, with fasting intervals ranging between 20 and 36 h. However, the long-term sustainability of this alternate day total fasting approach in human subjects is questionable due to the persistent hunger reported (24) .…”

Section: Overview and Effects On Body Weightmentioning

confidence: 99%

“…100 % energy restriction) every other day, with fasting intervals ranging between 20 and 36 h. However, the long-term sustainability of this alternate day total fasting approach in human subjects is questionable due to the persistent hunger reported (24) . Subsequently, the IER protocols used by most human studies (27)(28)(29)(30)(31)(32)(33)(34)(35)(36)(37)(38)(39)(40)(41) , and by some rodent studies (11,14,42) , have allowed a small amount of 'fast' day intake, so that energy is substantially (⩾70 %) but not completely restricted. This is often referred to as modified fasting, such that, the term fasting in this IER context denotes periods of severe (total or partial) energy restriction.…”

Section: Overview and Effects On Body Weightmentioning

confidence: 99%

“…The result is the creation of an unfavourable metabolic and hormonal milieu, which drives the development of systemic insulin resistance and associated metabolic disorders (46) . Several studies have shown that rodents maintained on IER exhibit reduced visceral adipose tissue (14,42) , as well as favourable reductions in fat cell size and augmented adipocyte differentiation within subcutaneous and visceral fat pads (11) . Levels of adiponectin, which has antiatherogenic and insulin-sensitising properties, are usually reduced in states of obesity but increased through IER (14,21) .…”

Section: Change In Adipose Tissue Morphology Physiology and Distribumentioning

confidence: 99%

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Effects of intermittent fasting on glucose and lipid metabolism

et al. 2017

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Two intermittent fasting variants, intermittent energy restriction (IER) and time-restricted feeding (TRF), have received considerable interest as strategies for weight-management and/or improving metabolic health. With these strategies, the pattern of energy restriction and/or timing of food intake are altered so that individuals undergo frequently repeated periods of fasting. This review provides a commentary on the rodent and human literature, specifically focusing on the effects of IER and TRF on glucose and lipid metabolism. For IER, there is a growing evidence demonstrating its benefits on glucose and lipid homeostasis in the short-to-medium term; however, more long-term safety studies are required. Whilst the metabolic benefits of TRF appear quite profound in rodents, findings from the few human studies have been mixed. There is some suggestion that the metabolic changes elicited by these approaches can occur in the absence of energy restriction, and in the context of IER, may be distinct from those observed following similar weight-loss achieved via modest continuous energy restriction. Mechanistically, the frequently repeated prolonged fasting intervals may favour preferential reduction of ectopic fat, beneficially modulate aspects of adipose tissue physiology/morphology, and may also impinge on circadian clock regulation. However, mechanistic evidence is largely limited to findings from rodent studies, thus necessitating focused human studies, which also incorporate more dynamic assessments of glucose and lipid metabolism. Ultimately, much remains to be learned about intermittent fasting (in its various forms); however, the findings to date serve to highlight promising avenues for future research.

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Effects of modified alternate-day fasting regimens on adipocyte size, triglyceride metabolism, and plasma adiponectin levels in mice

Cited by 75 publications

References 29 publications

Enhanced Metabolic Flexibility Associated with Elevated Adiponectin Levels

Enhanced Metabolic Flexibility Associated with Elevated Adiponectin Levels

Intermittent calorie restriction largely counteracts the adverse health effects of a moderate‐fat diet in aging C57BL/6J mice

Effects of intermittent fasting on glucose and lipid metabolism

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