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Metabolism during Fasting and Starvation: Understanding the Basics to Glimpse New Boundaries

Metabolism during Fasting and Starvation: Understanding the Basics to
Glimpse New Boundaries
Moacir Couto de Andrade Júnior1,2*
1Post-Graduation Department, Nilton Lins University, Manaus, Brazil
2Department of Food Technology, Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, Brazil
*Corresponding author: Andrade Jr MC, Department of Food Technology, Instituto Nacional de Pesquisas da Amazônia (INPA), Manaus, Brazil, Tel: +55 (92)
3633-8028; E-mail:
Received date: Sep 19, 2017; Accepted date: Sep 25, 2017; Published date: Sep 28, 2017
Copyright: © 2017 Andrade Jr MC. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted
use, distribution, and reproduction in any medium, provided the original author and source are credited.
e human diet is a complex mixture of interacting components
that cumulatively aect health [1]. e metabolizable energy of
macronutrients (i.e., carbohydrates, proteins, and lipids) is responsible
for the bulk of the energy in the human diet. Micronutrients (i.e.,
minerals and vitamins) play a central role in metabolism and in the
maintenance of tissue function [2]. Metabolism encompasses all of the
biochemical processes used by organisms to synthesize structural and
functional constituents and to obtain energy. It is typically divided into
anabolism, which includes the biosynthesis of macromolecules such as
glycogen, proteins, and lipids (e.g., triacylglycerol, TAG) and
catabolism, which includes the degradation of macromolecules into
their simplest precursors: glucose, amino acids, glycerol, and fatty
acids. e free energy released by catabolic degradation- via adenosine
triphosphate and nicotinamide adenine diphosphate- is used to drive
the endergonic processes of anabolic biosynthesis [3]. Carbohydrates
(e.g., glycogen) constitute immediate energy stores (liver), and lipids
(e.g., TAG) constitute long-term energy stocks (adipocytes) [4].
Proteins constitute the active (functional) cell mass and are a minor
source of energy [4].
Pancreatic insulin and pituitary growth hormone (GH)- via the
hepatic eector insulin-like growth factor-1 (IGF-1)- are examples of
anabolic hormones. Gastric ghrelin is another anabolic hormone that
stimulates appetite, other endocrine secretions (pituitary GH,
prolactin, and adrenocorticotropic hormone), and weight gain [5].
Androgens (e.g., testosterone) may have an anabolic eect (protein
synthesis) [6]. Anabolism increases the requirements for all nutrients,
including micronutrients, that should be supplied when patients are
gaining weight [2]. On the other hand, pancreatic glucagon and
adrenal epinephrine and cortisol are examples of catabolic
(hyperglycemic) hormones. ese hormones, together with GH,
counter-regulate hypoglycemia (i.e., a plasma glucose less than 70 mg/
dL). Pancreatic glucagon, in particular, stimulates the liver to release
glucose via glycogenolysis (i.e., the breakdown of glycogen) and
gluconeogenesis (i.e., glucose synthesis from non-glycosidic substrates)
and stimulates adipose tissue to release free fatty acids (FFAs) and
glycerol via lipolysis (i.e., the breakdown of TAG) [3]. yroid
hormones (e.g., triiodothyronine or T3) are catabolic and play an
important role over the long term in determining the set of
metabolism [6]. Adipocyte leptin is catabolic in nature and inhibits
food intake and lipid storage while promoting energy expenditure [7].
e catabolism associated with acute injury (e.g., infection, surgery, or
trauma) leads to elevated energy expenditure and protein breakdown,
increasing the requirements for vitamins and minerals [2,8]. At this
phase, anabolism is postponed in favor of catabolism [8].
ere is also amphibolic metabolism, so-called for serving both
anabolic as well as catabolic pathways. e enzymes (and their
substrates) of this bi-directional metabolism remain better studied in
prokaryotic organisms (bacteria) such as
Escherichia coli
, whose
teleonomy of certain strains enables metabolic versatility that is mainly
linked to the citric acid cycle, also known as tricarboxylic acid or the
Krebs cycle [9]. Other dynamic aspects of this vital metabolic cycle
include anaplerosis and cataplerosis; the rst term refers to the relling
of the Krebs cycle whenever an intermediate leaves the mitochondria
during biosynthetic events, and the second term refers to the opposite
function (i.e., the removal of accumulating citric acid cycle anions)
e fact that metabolism occurs in many stages mediated by
numerous enzyme substrates and products (metabolites) motivates the
term intermediate metabolism. e metabolism of macronutrients is
particularly interrelated [4]. For instance, glucose may be synthesized
from lactate, glycerol, and amino acids (e.g., alanine)
(gluconeogenesis), but not from fatty acids [4]. In contrast, the
dihydroxyacetone phosphate used to make glycerol-3-phosphate (G3P)
for TAG synthesis derives either from glucose via the glycolytic
pathway (or Embden-Meyerhof pathway) or from oxaloacetate via an
abbreviated version of gluconeogenesis termed glyceroneogenesis [3].
Importantly, both gluconeogenesis and glyceroneogenesis are
cataplerotic pathways because they convert citric acid cycle anions to
phosphoenolpyruvate, which is then used to make either glucose or
G3P [10].
It should be emphasized that glucose and FFAs are the most
important energy substrates for most organisms (including humans)
and that intermediate metabolism reects the primacy of these fuels.
Moreover, the existence of metabolic cycles such as glucose-lactate (the
Cori cycle), glucose-fatty acid (the Randle cycle), and glucose-alanine
(the Cahill cycle) reinforces this idea.
Each day, a human’s three primary meals are breakfast, lunch, and
dinner, which are interspersed by interprandial fasting periods of
approximately ve hours each. e longest fasting period corresponds
to nocturnal fasting (roughly eight hours). Sleep eectively imposes an
extended period of fasting during which energy metabolism diers
between sleep stages and begins to increase prior to awakening [11].
Fasting metabolism is clearly adapted to ensuring the orderly
mobilization of endogenous substrates and energy for maintaining
vital activity [12]. It is characterized by low insulin levels, high
glucagon levels, liver glycogenolysis, and gluconeogenesis for
maintaining serum glucose levels and cerebral function [13,14].
Fasting metabolism also involves high levels of lipolysis and FFAs via
circulating TAG for enabling energy utilization by most tissues other
than the brain and the central nervous system (CNS) [13,14]. Glucose
Journal of Nutrition and Dietetics
Andrade Jr, J Nutr Diet 2017, 1:1
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J Nutr Diet, an open access journal Volume 1 • Issue 1 • e02
then reaches the CNS through specic transporters (e.g., GLUT1 and
3) [15]. As fasting continues, progressive ketosis develops due to the
mobilization and β-oxidation of fatty acids and the increase in ketone
bodies (KBs) (e.g., β-hydroxybutyrate) that replace glucose as the
primary energy source in the CNS, thereby decreasing the need for
gluconeogenesis and sparing protein catabolism [3,16]. At this stage,
hormonal adaptive changes involve, for example, low insulin and T3
levels along with high levels of ketogenic glucagon and the inactive
metabolite of T3 (i.e., reverse T3 or rT3) [16]. Ketone bodies reach the
CNS via monocarboxylic acid transporters (e.g., MCT1 and 2) [15].
e brain and other organs utilize KBs in a process termed ketolysis
[17]. On the contrary, in the fed state, postprandial metabolism is
essentially characterized by high insulin levels responsible for both
antilipolytic and antigluconeogenic actions (by suppressing these two
pathways) and lipogenic actions (e.g., by stimulating the enzyme
lipoprotein lipase (EC, which hydrolyzes the TAG of
chylomicrons and very low-density lipoprotein at the endothelial
surface, which releases FFAs and glycerol for adipocyte storage)
[13,14,18]. Aquaglyceroporins (e.g., AQP7 and 9) are responsible for
transporting glycerol in the adipocytes [19]. erefore, insulin plays an
essential role in controlling energy metabolism in both a fasting state
(in which it prevents severe ketoacidosis) and also in a fed state (in
which it promotes fuel storage) [14,20]. Diabetic patients, especially
type 1 diabetics, may develop severe ketoacidosis due to a profound
insulin deciency [14].
Fasting oen refers to abstinence from food, and the term starvation
is used to describe a state of extreme hunger resulting from a
prolonged lack of essential nutrients [21]. Hence, the adaptive fasting
briey described above is an evolutionary tactic distinct from
starvation [22]. Starvation is, in principle, longer, potentially harmful,
and may lead to a lethal outcome. Additionally, fasting and starvation
are not synonymous terms, but the expression prolonged fasting is
used as a synonym to starvation in the literature. e response to
starvation is integrated at all levels of organization and is directed
toward the survival of the species [21]. Hunger is an adaptive response
to food deprivation that involves sensory, cognitive, and
neuroendocrine changes (e.g., increased neuropeptide Y or NPY) that
motivate and enable food-seeking behavior [17]. As carbohydrate
reserves are rapidly depleted, and protein sources are minor, the
survival period of starving individuals depends more on fat reserves
than on muscle mass (e.g., obese individuals can survive for several
months without eating in clinically supervised weight-reduction
programs) [3,4,16]. Apart from the rapidly depleted hepatic
glycogenolysis, the other major metabolic pathways of energy supply
supplement one other during prolonged fasting or starvation (Figure
1). e increased serum rT3 and the decreased T3 lead to conservation
of energy and a decrease in protein breakdown [23]. e increase in
renal gluconeogenesis is accompanied by an augmentation in
ammonia formation, as evidenced by the increased urinary excretion
of ammonia [14,20]. Nevertheless, adipocyte lipolysis (with weight
loss) for liver ketogenesis becomes the most prominent interrelated
metabolic pathway during starvation [14,20]. If starvation continues
until the adipose stores are depleted, muscle is rapidly degraded for
gluconeogenesis, potentially leading to a lethal outcome [14,20,22].
Figure 1: Simplied overview of the hormonal and metabolic
alterations during food deprivation. Note: , low; , high; CATs,
catecholamines (epinephrine and norepinephrine). Plasma CATs
are unchanged aer 36 hours of fasting, but they are signicantly
increased aer 72 hours of fasting [24]. Glucose-6-phosphatase (EC is an enzyme found mainly in the liver and the kidneys [25].
It plays the important role of providing glucose during starvation
It is possible to glimpse the new boundaries to which the
metabolism of starvation has been placed. Critical illness represents a
multifarious cellular insult with damage induced by hypoxia,
hypoperfusion, and inammation, and the removal of cell damage by
autophagy is essential for recovery [26]. Autophagy is an evolutionarily
conserved process that degrades cellular components to restore energy
homeostasis under limited nutrient conditions such as starvation [27].
us, starvation promotes autophagy [28]. On the contrary,
suppressive eects by nutrients early during critical illness could
compromise such damage removal systems [26]. How this starvation-
induced autophagy is regulated at the whole-body level is not entirely
understood yet [27]. However, anabolic hormones (e.g., insulin and
IGF-1) and catabolic hormones (e.g., glucagon and CATs) are
signicant regulators of autophagy [29].
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... Glyceroneogenesis is defined as de novo synthesis of glycerol-3-phosphate from pyruvate, lactate, and certain amino acids [86]. It is correctly considered an abbreviated version of gluconeogenesis (i.e., glucose synthesis from nonglycosidic substrates) [87]. Glycerol metabolism is closely associated with that of carbohydrates [81,85,87]. ...
... It is correctly considered an abbreviated version of gluconeogenesis (i.e., glucose synthesis from nonglycosidic substrates) [87]. Glycerol metabolism is closely associated with that of carbohydrates [81,85,87]. ...
... In the fed state, postprandial metabolism is essentially characterized by high insulin levels that are responsible for antilipolytic action (e.g., by inhibiting HSL) and antigluconeogenic action (by suppressing this metabolic pathway) as well as for lipogenic action (e.g., by stimulating LPL) [87,117]. Human insulin is a 51-amino acid peptide hormone that is produced by pancreatic β-cells in addition to be a major regulator of LPL activity (Figure 3) [110,118]. ...
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Carbohydrates (e.g., glucose) and lipids (e.g., free fatty acids or FFAs) are the most important sources of energy for most organisms, including humans. Lipoprotein lipase (LPL) is an extracellular enzyme (EC that is essential in lipoprotein metabolism. LPL is a glycoprotein that is synthesized and secreted in several tissues (e.g., adipose tissue, skeletal muscle, cardiac muscle, and macrophages). At the luminal surface of the vascular endothelium (site of the enzyme action), LPL hydrolyzes triglyceride-rich lipoproteins (e.g., chylomicrons, very lowdensity lipoproteins), providing FFAs and glycerol for tissue use. Therefore, LPL plays a key metabolic role in providing substrates for lipogenesis and lipid storage, and in supplying immediate energy for different tissues. Knowledge about this enzyme has greatly increased over the past decade. A detailed understanding of the fascinating, although complex, apparatus by which LPL exerts its catalytic activity in the turbulent bloodstream is just one of the examples. Additionally, interest in LPL activity has been reinforced by its pathophysiological relevance in chronic degenerative diseases such as dyslipidemia, obesity, type 2 diabetes mellitus, and Alzheimer's disease, and in other contexts of disordered lipid metabolism such as severe hypertriglyceridemia and the (potentially) associated acute pancreatitis as well as in non-alcoholic fatty liver disease. This work aimed at critically reviewing the current knowledge of historical, terminological, biochemical, pathophysiological, and therapeutic aspects of human LPL activity.
... Prior to the exercise session, animals from the FAR and FAE groups were subjected to a fasting period of 8 h [45]. The acute exercise consisted of a 30 min session on the treadmill, with speed and inclination corresponding to an intensity of 60% of VO2max (10 m/min, 0° treadmill grade), according to Rodrigues et al. [24]. ...
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Introduction and objectives: Obesity represents a major global public health problem. Its etiology is multifactorial and includes poor dietary habits, such as hypercaloric and hyperlipidic diets (HFDs), physical inactivity, and genetic factors. Regular exercise is, per se, a tool for the treatment and prevention of obesity, and recent studies suggest that the beneficial effects of exercise can be potentiated by the fasting state, thus potentially promoting additional effects. Despite the significant number of studies showing results that corroborate such hypothesis, very few have evaluated the effects of fasted-state exercise in overweight/obese populations. Therefore, the aim of this study was to evaluate the subacute effects (12 h after conclusion) of a single moderate-intensity exercise bout, performed in either a fed or an 8 h fasted state, on serum profile, substrate-content and heat shock pathway-related muscle protein immunocontent in obese male rats. Methods: Male Wistar rats received a modified high-fat diet for 12 weeks to induce obesity and insulin resistance. The animals were allocated to four groups: fed rest (FER), fed exercise (FEE), fasted rest (FAR) and fasted exercise (FAE). The exercise protocol was a 30 min session on a treadmill, with an intensity of 60% of VO2max. The duration of the fasting period was 8 h prior to the exercise session. After a 12 h recovery, the animals were killed and metabolic parameters of blood, liver, heart, gastrocnemius and soleus muscles were evaluated, as well as SIRT1 and HSP70 immunocontent in the muscles. Results: HFD induced obesity and insulin resistance. Soleus glycogen concentration decreased in the fasted groups and hepatic glycogen decreased in the fed exercise group. The combination of exercise and fasting promoted a decreased concentration of serum total cholesterol and triglycerides. In the heart, combination fasting plus exercise was able to decrease triglycerides to control levels. In the soleus muscle, both fasting and fasting plus exercise were able to decrease triglyceride concentrations. In addition, heat shock protein 70 and sirtuin 1 immunocontent increased after exercise in the gastrocnemius and soleus muscles. Conclusions: An acute bout of moderate intensity aerobic exercise, when realized in fasting, may induce, in obese rats with metabolic dysfunctions, beneficial adaptations to their health, such as better biochemical and molecular adaptations that last for at least 12 h. Considering the fact that overweight/obese populations present an increased risk of cardiovascular events/diseases, significant reductions in such plasma markers of lipid metabolism are an important achievement for these populations. Citation: Vogt, É.L.; Von Dentz, M.; Rocha, D.S.; Model, J.F.A.; Kowalewski, L.S.; de Souza, S.; Girelli, V.; de Bittencourt, P., Jr.; Friedman, R.; et al. Metabolic and Molecular Subacute Effects of a Single Moderate-Intensity Exercise Bout, Performed in the Fasted State, in Obese Male Rats. Int. J. Environ.
... It is hypothesised that the rats which were at approximately 12 weeks old on Day 15 had higher growing rate. Higher activity and metabolism rate were experienced, and higher nutrient requirement was observed (as showed in Figure 1) compared to Day 0. As a consequence, elevated 3-hydroxybutyrate, glucose and lactate, the metabolic products of ketogenesis and gluconeogenesis might indicate higher metabolic activity and fasting experienced prior to blood collection [26,27]. ...
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The present study aims for the first time to provide the in vivo acute toxicological profile of the highest dose of Clinacanthus nutans (Burm. f.) Lindau water leaf extract according to the Organization for economic co-operation and development (OECD) 423 guidelines through conventional toxicity and advanced proton nuclear magnetic resonance (1H-NMR) serum and urinary metabolomics evaluation methods. A single dose of 5000 mg/kg bw of C. nutans water extract was administered to Sprague Dawley rats, and they were observed for 14 days. Conventional toxicity evaluation methods (physical observation, body and organ weight, food and water consumption, hematology, biochemical testing and histopathological analysis) suggested no abnormal toxicity signs. Serum 1H-NMR metabolome revealed no significant metabolic difference between untreated and treated groups. Urinary 1H-NMR analysis, on the other hand, revealed alteration in carbohydrate metabolism, energy metabolism and amino acid metabolism in extract-treated rats after 2 h of extract administration, but the metabolic expression collected after 24 h and at Day 5, Day 10 and Day 15 indicated that the extract-treated rats did not accumulate any toxicity biomarkers. Importantly, the outcomes further suggest that single oral administration of up to 5000 mg/kg bw of C. nutans water leaf extract is safe for consumption.
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Background and Objective: Lactation ketoacidosis is a rare cause of high anion gap metabolic acidosis affecting breastfeeding mothers. We aim to review and analyze all cases of lactation ketoacidosis reported. Materials and Methods: A systematic search of PubMed/MEDLINE and Cumulative Index to Nursing and Allied Health Literature (CINAHL), identifying relevant case reports published from 1 January 1970 to 31 December 2019. We extracted the following data: the first author, country, year of publication, age of the mother, age of the child, weight/body mass index (BMI) of the mother, precipitating factors, presenting symptoms, biochemical results, treatment, breastfeeding, and time from presentation to the resolution of ketoacidosis. Results: Sixteen case reports and 1 case series reporting 18 cases of lactation ketoacidosis were found. Presenting symptoms were nausea (72%, 13/18), vomiting (67%, 12/18), malaise (56%, 10/18), abdominal pain (44%, 8/18), dyspnea (33%, 6/18), headache (22%, 4/18), and palpitation (11%, 2/18). Dieting and physical exercise to lose weight were reported in 76% (14/18). The treatments included IV dextrose, sodium bicarbonate, insulin, rehydration, monitoring and replacement of electrolytes, and resumption of a balanced diet. The prognoses were good, with no mortalities. Conclusions: lactation ketoacidosis should be suspected in unwell breastfeeding women with high anion gap metabolic acidosis, after excluding other causes.
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Autophagy is an evolutionarily conserved process that degrades cellular components to restore energy homeostasis under limited nutrient conditions. How this starvation-induced autophagy is regulated at the whole-body level is not fully understood. Here, we show that the tumor suppressor Lkb1, which activates the key energy sensor AMPK, also regulates starvation-induced autophagy at the organismal level. Lkb1-deficient zebrafish larvae fail to activate autophagy in response to nutrient restriction upon yolk termination, shown by reduced levels of the autophagy-activating proteins Atg5, Lc3-II and Becn1, and aberrant accumulation of the cargo receptor and autophagy substrate p62. We demonstrate that the autophagy defect in lkb1 mutants can be partially rescued by inhibiting mTOR signaling but not by inhibiting the PI3K pathway. Interestingly, mTOR-independent activation of autophagy restores degradation of the aberrantly accumulated p62 in lkb1 mutants and prolongs their survival. Our data uncover a novel critical role for Lkb1 in regulating starvation-induced autophagy at the organismal level, providing mechanistic insight into metabolic adaptation during development.
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Brain cells normally respond adaptively to bioenergetic challenges resulting from ongoing activity in neuronal circuits, and from environmental energetic stressors such as food deprivation and physical exertion. At the cellular level, such adaptive responses include the "strengthening" of existing synapses, the formation of new synapses, and the production of new neurons from stem cells. At the molecular level, bioenergetic challenges result in the activation of transcription factors that induce the expression of proteins that bolster the resistance of neurons to the kinds of metabolic, oxidative, excitotoxic, and proteotoxic stresses involved in the pathogenesis of brain disorders including stroke, and Alzheimer's and Parkinson's diseases. Emerging findings suggest that lifestyles that include intermittent bioenergetic challenges, most notably exercise and dietary energy restriction, can increase the likelihood that the brain will function optimally and in the absence of disease throughout life. Here, we provide an overview of cellular and molecular mechanisms that regulate brain energy metabolism, how such mechanisms are altered during aging and in neurodegenerative disorders, and the potential applications to brain health and disease of interventions that engage pathways involved in neuronal adaptations to metabolic stress.
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The contribution of thyroidal status in insulin signaling and glucose homeostasis has been implicated as a potential pathophysiological factor in humans, but the specific mechanisms remain largely elusive. Fasting induces changes in both thyroid hormone secretion and insulin signaling. Here, we explore how mammals that undergo natural, prolonged bouts of fasting provide unique insight into evolved physiological adaptations that allow them to tolerate such conditions despite intermittent states of reversible insulin resistance. Such insights from nature may provide clues to better understand the basis of thyroidal involvement in insulin dysregulation in humans.
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Dietary Reference Intakes (DRIs) are used in Canada and the United States in planning and assessing diets of apparently healthy individuals and population groups. The approaches used to establish DRIs on the basis of classical nutrient deficiencies and/or toxicities have worked well. However, it has proved to be more challenging to base DRI values on chronic disease endpoints; deviations from the traditional framework were often required, and in some cases, DRI values were not established for intakes that affected chronic disease outcomes despite evidence that supported a relation. The increasing proportions of elderly citizens, the growing prevalence of chronic diseases, and the persistently high prevalence of overweight and obesity, which predispose to chronic disease, highlight the importance of understanding the impact of nutrition on chronic disease prevention and control. A multidisciplinary working group sponsored by the Canadian and US government DRI steering committees met from November 2014 to April 2016 to identify options for addressing key scientific challenges encountered in the use of chronic disease endpoints to establish reference values. The working group focused on 3 key questions: 1) What are the important evidentiary challenges for selecting and using chronic disease endpoints in future DRI reviews, 2) what intake-response models can future DRI committees consider when using chronic disease endpoints, and 3) what are the arguments for and against continuing to include chronic disease endpoints in future DRI reviews? This report outlines the range of options identified by the working group for answering these key questions, as well as the strengths and weaknesses of each option.
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Autophagy is a cellular quality control and energy-providing process that is under strict control by intra- and extra-cellular stimuli. Recently, there has been an exponential increase in autophagy research and its implications for mammalian physiology. Autophagy de-regulation now is being implicated in many human diseases and its modulation has shown promising results in several pre-clinical studies. However, despite its first discovery as a hormone-regulated process by de Duve in the early 1960's, endocrine regulation of autophagy still remains poorly understood. In this review, we provide a critical summary of our present understanding of the basic mechanism of autophagy, its regulation by endocrine hormones, and its contribution to endocrine and metabolic homeostasis under physiological and pathological settings. Understanding the cross-regulation of hormones and autophagy on endocrine cell signaling and function will provide new insight into mammalian physiology as well as promote the development of new therapeutic strategies involving modulation of autophagy in endocrine and metabolic disorders.
Background Type 2 diabetes is associated with excess postprandial lipemia due to accumulation of chylomicrons and VLDL particles. This is a risk factor for development of cardiovascular disease. However, whether the excess lipemia is associated with an impaired suppression of VLDL-TG secretion and/or reduced clearance into adipose tissue is unknown. Objective We measured the postprandial VLDL-TG secretion, clearance and adipose tissue storage to test the hypothesis that impaired postprandial suppression of VLDL-TG secretion, combined with impaired VLDL-TG storage in adipose tissue, is associated with excess postprandial lipemia. Design We studied 11 men with type 2 diabetes and 10 weight-matched non-diabetic men using ex-vivo labeled VLDL-TG tracers during an oral high-fat mixed-meal tolerance test to measure postprandial VLDL-TG secretion, clearance and storage. In addition, adipose tissue biopsies were analyzed for LPL activity and cellular storage factors. Results Men with type 2 diabetes had greater postprandial VLDL-TG concentration compared to non-diabetic men. However, postprandial VLDL-TG secretion rate was similar in the two groups with equal suppression of VLDL-TG secretion rate (≈50%) and clearance rate. In addition, postprandial VLDL-TG storage was similar in the two groups in both upper body and lower body subcutaneous adipose tissue. Conclusions Despite greater postprandial VLDL-TG concentration, men with type 2 diabetes have similar postprandial suppression of VLDL-TG secretion and a similar ability to store VLDL-TG in adipose tissue compared to non-diabetic men. This may indicate that abnormalities in postprandial VLDL-TG metabolism are a consequence of obesity/insulin resistance more than a result of type 2 diabetes per se.
Objective: An inhibitory effect of ghrelin on gonadotrophin secretion has been reported in normally menstruating women possibly modulated by endogenous estrogen. The aim of this study was to examine the effect of ghrelin on gonadotrophin and PRL secretion in estrogen-deprived postmenopausal women. Design: Prospective intervention study. Patients and measurements: Ten healthy postmenopausal volunteer women were studied during two 15-day periods of estrogen treatment (A and B) a month apart. Four experiments (Exp) were performed in total, two on day 1 (Exp 1A and Exp 1B) and two on day 15 (Exp 15A and Exp 15B) of the two periods. The women received in Exp 1A and in Exp 15A two iv injections of ghrelin (0.15 μg/kg at time 0 min and 0.30 μg/kg at time 90 min) and in Exp1B and in Exp 15B normal saline (2 ml) respectively. Blood samples were taken at -15, 0, 30,60, 90, 120, 150 and 180 min. Results: After estrogen treatment, late follicular phase serum estradiol levels were attained on day 15 of periods A and B. Ghrelin administration did not affect serum levels of FSH and LH, whereas it increased significantly those of GH and PRL. In Exp 15A, serum PRL increment in response to ghrelin (area under the curve, net increment) was significantly greater than in Exp 1A (P<0.05). Conclusions: The present study demonstrates for the first time that in estrogen-deprived postmenopausal women, ghrelin administration affects neither FSH nor LH levels but stimulates PRL secretion, that is amplified by exogenous estrogen administration. This article is protected by copyright. All rights reserved.
Purpose: Human sleep is generally consolidated into a single prolonged period, and its metabolic consequence is to impose an extended period of fasting. Changes in sleep stage and homeostatic sleep drive following sleep onset may affect sleeping metabolic rate through cross talk between the mechanisms controlling energy metabolism and sleep. The purpose of this study was to isolate the effects of sleep stage and time after sleep onset on sleeping metabolic rate. Methods: The sleeping metabolic rate of 29 healthy adults was measured using whole room indirect calorimetry, during which polysomnographic recording of sleep was performed. The effects of sleep stage and time after sleep onset on sleeping metabolic rate were evaluated using a semi-parametric regression analysis. A parametric analysis was used for the effect of sleep stage and a non-parametric analysis was used for the effect of time. Results: Energy expenditure differed significantly between sleep stages: wake after sleep onset (WASO)>stage 2, slow wave sleep (SWS), and REM; stage 1>stage 2 and SWS; and REM>SWS. Similarly, carbohydrate oxidation differed significantly between sleep stages: WASO > stage 2 and SWS; and stage 1>SWS. Energy expenditure and carbohydrate oxidation decreased during the first half of sleep followed by an increase during the second half of sleep. Conclusions: This study identified characteristic phenotypes in energy expenditure and carbohydrate oxidation indicating that sleeping metabolic rate differs between sleep stages.
Purpose of review: Anorexia is a preserved evolutionally response that may be beneficial during acute illness. Yet current clinical practice guidelines recommend early and targeted enteral nutritional support. However, the optimal timing of the initiation of enteral nutrition and the caloric and protein requirements of critically ill patients is controversial. Recent findings: Starvation promotes autophagy and this may play a key role in promoting host defenses and the immune response to intracellular pathogens. Because of the perceived benefits of early enteral nutrition and the lack of clinical equipoise, randomized controlled trials comparing short-term starvation to targeted normocaloric enteral nutrition have until recently not been performed. The results of the recently reported PYTHON trial (Pancreatitis, Very Early Compared with Selective Delayed Start of Enteral Feeding) dispel the notion that short-term starvation is harmful. Furthermore, six recent randomized controlled trials that compared trophic and permissive underfeeding to normocaloric goals, failed to demonstrate any outcome benefit from the more aggressive approach. In addition, recent evidence suggests that intermittent enteral nutation may be preferable to continuous tube feeding. Summary: Limiting nutrient intake during the first 48-72 h of acute illness may be beneficial; in those patients who are unable to resume an oral diet after this time period intermittent enteral nutrition targeting 20-25 cal/kg/day is recommended.