Caloric Deprivation Research Articles

Dietary fat content and absorption shape standard diet devaluation through hunger circuits

ObjectiveExposure to 60% high fat diet (HFD) leads to a robust consummatory preference over well-balanced chow standard diet (SD) when mice are presented with a choice. This passive HFD-induced SD devaluation following HFD challenge and withdrawal is highlighted by the significant reduction in SD food intake even in states of caloric deprivation. The elements of HFD that lead to this SD depreciation remains unclear. Possibly important factors include the amount and type of fat contained in a diet as well as past eating experiences dependent on sensory properties including taste and post ingestive feedback. We aimed to explore the role of these components to HFD-induced SD devaluation. MethodsWildtype mice were longitudinally presented discrete HFDs in conjunction with SD and feeding and metabolic parameters were analyzed. A separate cohort of animals were assessed for acute HFD preference in 3 conditions: 1) ad libitum fed (sated), 2) overnight fasted (physiologically hungry), and 3) ad libitum fed (artificially hungry), elicited through chemogenetic Agouti-related peptide (AgRP) neuron activation. Population dynamics of AgRP neurons were recorded to distinct inaccessible and accessible diets both before and after consummatory experience. Transient receptor potential channel type M5 (TRPM5) knockout mice were used to investigate the role of fat taste perception and preference to HFD-induced SD devaluation. The clinically approved lipase inhibitor orlistat was used to test the contribution of fat absorption to HFD-induced SD devaluation. ResultsHFD-induced SD devaluation is dependent on fat content, composition, and preference. This effect scaled both in strength and latency with higher percentages of animal fat. 60% HFD was preferred and almost exclusively consumed in preference to other diets across hours and days, but this was not as evident upon initial introduction over seconds and minutes, suggesting ingestive experience is critical. Optical fiber photometry recordings of AgRP activity supported this notion as neuronal suppression by the different diets was contingent on prior intake. While taste transduced via TRPM5 influenced HFD-evoked weight gain, it failed to impact either HFD preference or HFD-induced SD devaluation. Perturbation of post ingestive feedback through orlistat-mediated diminishment of fat absorption prevented HFD-evoked weight gain and abolished HFD-induced SD devaluation. ConclusionsPost ingestive feedback via fat digestion is vital for expression of HFD-induced SD devaluation.

The Self-Control of Eating.

Many individuals struggle to regulate their own consumption of food. Beginning with general theories of self-control, we review psychological factors that have been shown to influence the regulation of eating, including those related to particular personality variables, such as external eating, restrained eating, and reward sensitivity, as well as situational constraints, including normative influences, emotions, and calorie deprivation. Strategies for the self-control of eating, including reappraisal, effortful inhibition, and various automatic strategies are also reviewed, along with a discussion of the strengths and limitations of historical and contemporary psychological studies investigating food consumption. Whereas extensive examinations of food preferences and body weight have appeared in the psychological literature, we call for more robust research that prioritizes actual eating as the primary dependent measure.

Total and H-specific GDF-15 levels increase in caloric deprivation independently of leptin in humans

Mitochondrial-secreted growth differentiation factor-15 (GDF-15) promotes weight loss in animals. Its effects in humans remain unclear, due to limited research and potential measurement interference from the H202D-variant. Our post-hoc analysis investigates total (irrespective of genetic variants) and H-specific GDF-15 (detected only in H202D-variant absence) in humans under acute and chronic energy deprivation, examining GDF-15 interaction with leptin (energy homeostasis regulator) and GDF-15 biologic activity modulation by the H202D-variant. Total and H-specific GDF-15 increased with acute starvation, and total GDF-15 increased with chronic energy deprivation, compared with healthy subjects and regardless of leptin repletion. Baseline GDF-15 positively correlated with triglyceride-rich particles and lipoproteins. During acute metabolic stress, GDF-15 associations with metabolites/lipids appeared to differ in subjects with the H202D-variant. Our findings suggest GDF-15 increases with energy deprivation in humans, questioning its proposed weight loss and suggesting its function as a mitokine, reflecting or mediating metabolic stress response.

Do early indicators of euthyroid sick syndrome predict later post-bariatric weight loss? Exploring a novel hypothesis

Despite bariatric surgery’s success for most patients, up to 30 % do not experience optimal weight loss outcomes. Post-surgery weight loss outcomes are influenced by a complex interplay of factors that remain incompletely understood. Novel hypotheses are needed to identify putative predictors of suboptimal post-bariatric weight loss. Thyroid hormones, due to their important role in energy expenditure, have received study though research to date has not established clear associations between post-surgical weight loss and changes in standard thyroid markers. In contrast, research consistently documents a pattern similar to euthyroid sick syndrome (ESS) during severe caloric deprivation or fasting. ESS, an established response to periods of stress (e.g., critical illness, infection, famine) is believed to serve a protective function by suppressing metabolism and conserving weight. Defining features of ESS are: 1) TSH levels within normal range; 2) abnormally low levels of the metabolically active form of thyroid hormone, or freetriiodothyronine (FT3); 3) abnormally high levels of the metabolically inactive reverse3,3′,5′-triiodothyronine (rT3); and 4) abnormally low ratios of FT3 to rT3. Low FT3/rT3 ratio levels significantly predict survival outcomes in ESS. We present the novel hypothesis that: 1) severe hypocaloric dieting during the early post-surgical period may trigger an ESS-like syndrome; 2) development of ESS will be signaled by a decrease in the FT3/rT3 ratio; and 3) early decreases in the FT3/rT3 ratio will be associated with reduced weight loss at standard 1- and 2-year post-surgical follow-up visits. To examine whether preliminary data might support our hypothesis, we undertook a small exploratory study by collecting TSH, FT4,FT3, rT3,and hypothyroid symptoms from adult patients undergoing Roux-en-Y gastric bypass (n = 12) or sleeve gastrectomy (n = 11). Body mass index was measured pre-surgery and 1- and 2-years post-surgery. Results showed reductions in the FT3:rT3ratio from pre- to early post-surgery significantly predicted reduced weight loss at 1 (p = 0.03) and 2 years(p = 0.02)post-surgery. No other thyroid-related markers nor symptoms were predictive. Replication with larger samples is needed, especially given our sizeable attrition at 1- and 2-year follow-up. In conclusion, our hypothesis that markers of ESS during the early post-surgical period would predict reduced longer-term weight loss was supported. If replicated in future, larger investigations, a practical application of this hypothesis-generating paper involves using the FT3:rT3 ratio to identify post-bariatric patients at risk for longer-term suboptimal weight loss, potentially opening a key therapeutic window for therapeutic intervention (e.g., T3 repletion).

The Beneficial and Adverse Effects of Autophagic Response to Caloric Restriction and Fasting.

Each cell is equipped with a conserved housekeeping mechanism, known as autophagy, to recycle exhausted materials and dispose of injured organelles via lysosomal degradation. Autophagy is an early-stage cellular response to stress stimuli in both physiological and pathological situations. It is thought that the promotion of autophagy flux prevents host cells from subsequent injuries by removing damaged organelles and misfolded proteins. As a correlate, the modulation of autophagy is suggested as a therapeutic approach in diverse pathological conditions. Accumulated evidence suggests that intermittent fasting or calorie restriction can lead to the induction of adaptive autophagy and increase longevity of eukaryotic cells. However, prolonged calorie restriction with excessive autophagy response is harmful and can stimulate a type II autophagic cell death. Despite the existence of a close relationship between calorie deprivation and autophagic response in different cell types, the precise molecular mechanisms associated with this phenomenon remain unclear. Here, we aimed to highlight the possible effects of prolonged and short-term calorie restriction on autophagic response and cell homeostasis.

Total and Intact GDF-15 Increase with Caloric Deprivation Independently of Leptin and are Associated with Starvation-induced Metabolomic Responses

Total and Intact GDF-15 Increase with Caloric Deprivation Independently of Leptin and are Associated with Starvation-induced Metabolomic Responses

A novel approach to measure poverty based on calorie deprivation - Evidence from household-level data

A novel approach to measure poverty based on calorie deprivation - Evidence from household-level data

Changes in serum cortisol levels after 10 days of overfeeding and fasting.

Chronic caloric deprivation and obesity are complicated by hypercortisolemia. The effects of acute overfeeding and fasting on circulating free cortisol levels and conversion of cortisone to free cortisol are unknown. We hypothesized that serum-free cortisol and free cortisol-to-cortisone ratio would increase after both overfeeding and fasting. This is a prospective study of 22 healthy volunteers who completed a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-wk washout. Morning free and total cortisol and free cortisone levels (LC/MS) were measured at baseline and after 10 days of each intervention. Both high-calorie feeding and fasting increased total and free cortisol and the free cortisol-to-free cortisone ratio (P = 0.001 to P = 0.046). There were sex interactions, with significant effects in men (P < 0.001), but not in women (P = 0.898 and 1.000, respectively) in subset analyses examining the effects of fasting on free cortisol and the free-to-total cortisol ratio. Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility.NEW & NOTEWORTHY Overfeeding and fasting both increase circulating free cortisol levels and appear to alter the balance between cortisol and its inactive metabolite, cortisone. The effect of fasting on free cortisol levels is modified by sex. Further study is needed to determine the mechanisms driving the increases in cortisol.

N-arachidonylglycine is a caloric state-dependent circulating metabolite which regulates human CD4+T cell responsiveness

Caloric deprivation interventions such as intermittent fasting and caloric restriction ameliorate metabolic and inflammatory disease. As a human model of caloric deprivation, a 24-h fast blunts innate and adaptive immune cell responsiveness relative to the refed state. Isolated serum at these time points confers these same immunomodulatory effects on transformed cell lines. To identify serum mediators orchestrating this, metabolomic and lipidomic analysis was performed on serum extracted after a 24-h fast and re-feeding. Bioinformatic integration with concurrent peripheral blood mononuclear cells RNA-seq analysis implicated key metabolite-sensing GPCRs in fasting-mediated immunomodulation. The putative GPR18 ligand N-arachidonylglycine (NAGly) was elevated during fasting and attenuated CD4+T cell responsiveness via GPR18 MTORC1 signaling. In parallel, NAGly reduced inflammatory Th1 and Th17 cytokines levels in CD4+T cells isolated from obese subjects, identifying a fasting-responsive metabolic intermediate that may contribute to the regulation of nutrient-level dependent inflammation associated with metabolic disease.

Effects of Mineral and Vitamin Supplementation on Swimming Times and Other Parameters Related to Performance of Rats on a Low Calorie Regimen

The effect of mineral and vitamin supplementation was studied on certain performance characteristics of rats on a low calorie, semipurified diet regimen. Male, albino, rats of the Charles River strain, 6 months old, were used. At a one-third ad libitum caloric level or less, the rats at nonsupplemented mineral-vitamin levels, on the whole, swam 26% longer than the groups receiving additional minerals and vitamins. This trend was the same with a low fat diet with corn oil and a relatively high fat diet with butter as the fat source. Lifespan was not affected at the 5% probability level by the mineral-vitamin supplementation used. A significant difference in blood glucose levels between rats receiving mineral-vitamin supplements versus those receiving none was found only after 10 days with one-third ad libitum caloric intake plus 9 days of complete caloric deprivation. However, the pooled results of blood glucose measurements during the whole period of caloric restriction showed no significant effect of the mineral-vitamin supplementation used. Likewise, water consumption was not significantly affected by mineral-vitamin supplementation. The same was true for weight loss.

ODP053 Serum Free Cortisol and Free Cortisol-to-Cortisone Ratio Increase After 10 Days of Overfeeding and After 10 Days of Fasting

Abstract Introduction Chronic caloric deprivation and obesity are complicated by elevations of serum total cortisol levels. The effects of acute overfeeding and fasting on circulating free cortisol levels and interconversion of cortisone to free cortisol are unknown. We hypothesized that serum free cortisol and free cortisol-to-cortisone ratio (a surrogate measure of 11β-hydroxysteroid dehydrogenase [11β-HSD] activity) would increase after both overfeeding and fasting. Methods We prospectively studied 22 healthy volunteers who underwent a 10-day high-calorie protocol followed by a 10-day fast, separated by a 2-week wash-out period, in a Clinical Research Center. Fasting morning free and total cortisol and free cortisone levels (liquid chromatography-tandem mass spectrometry, Mayo Labs) and percent body fat (dual-energy x-ray absorptiometry) were performed at baseline before and after 10 days of each intervention. Results High-calorie feeding increased total and free cortisol and the free cortisol-to-free cortisone ratio (p&amp;lt;0. 001 to p=0. 046). Total and free cortisol, the free cortisol-to-free cortisone ratio, and the free cortisol-to-total cortisol ratio increased after fasting (p=0. 001 to 0. 021). During the high-calorie protocol, there was no significant interaction between sex and time for any of the cortisol parameters. During the fasting visit, the changes in free cortisol and free-to-total cortisol ratio were modified by sex (p=0. 014 and 0. 004, respectively for interaction term), with a trend toward a significant interaction between sex and time in the change in free cortisol-to-free cortisone ratio (p=0. 054). In subset analyses stratified by sex examining the effect of fasting on free cortisol and the free-to-total cortisol ratio, there were significant increases in men (p&amp;lt;0. 001) but not women (p=0.898 and 1. 000, respectively). Baseline percent body fat, measured at the start of the fasting visit, was inversely associated with change in free cortisol (ρ=-0.52, p=0. 013), free cortisol-to-total cortisol ratio (ρ=-0.49, p=0. 021) and free cortisol-to-cortisone ratio (ρ=-0.47, p=0. 029) during fasting. Conclusion Overfeeding and fasting both increase circulating free cortisol levels and appear to alter 11β-HSD activity. The effect of fasting, but not overfeeding, on free cortisol levels is modified by sex. Greater percent fat mass may be relatively protective against starvation-induced hypercortisolemia in women. Further study is warranted to determine whether elevated cortisol levels contribute to complications of starvation and obesity, such as bone fragility. Presentation: No date and time listed

Comparing healthy adolescent females with and without parental history of eating pathology on neural responsivity to food and thin models and other potential risk factors.

We tested the hypotheses that female adolescents at risk for future eating disorders, based on parental history of binge eating and compensatory weight control behaviors, would show greater reward and attention region response to thin-models and tastes, anticipated tastes, and images of high-calorie foods, lower inhibitory circuitry response to a high-calorie food-specific go/no-go paradigm, and greater limbic circuitry response to negative mood induction. We recruited female adolescents free of binge eating or compensatory behaviors (N = 88; Mage = 14.6 [SD = .9]; 72% White) with versus without parental history of eating pathology. Parental-history-positive youth showed elevated reward region response (putamen) to anticipated tastes of chocolate milkshake, and greater emotionality, caloric deprivation, weight and shape overvaluation, and feeling fat (though no difference in weight), but lower liking of high-calorie foods, which were medium to large effects. We did not observe statistically significant differences in neural responsivity for the other paradigms. The evidence that parental-history-positive youth show greater reward region response to anticipated tastes of high-calorie food, overvaluation of weight/shape, feeling fat, caloric deprivation, emotionality, and lower liking of high-calorie foods before evidencing behavioral symptoms of eating disorders are novel findings. Weight/shape overvaluation may contribute to feeling fat, lower food liking, and caloric deprivation; the latter may drive elevated reward region response to anticipated consumption of high-calorie food and emotionality. (PsycInfo Database Record (c) 2021 APA, all rights reserved).

The dynamics of human bone marrow adipose tissue in response to feeding and fasting.

BACKGROUNDAdipocytes were long considered inert components of the bone marrow niche, but mouse and human models suggest bone marrow adipose tissue (BMAT) is dynamic and responsive to hormonal and nutrient cues.METHODSIn this study of healthy volunteers, we investigated how BMAT responds to acute nutrient changes, including analyses of endocrine determinants and paracrine factors from marrow aspirates. Study participants underwent a 10-day high-calorie protocol, followed by a 10-day fast.RESULTSWe demonstrate (a) vertebral BMAT increased significantly during high-calorie feeding and fasting, suggesting BMAT may have different functions in states of caloric excess compared with caloric deprivation; (b) ghrelin, which decreased in response to high-calorie feeding and fasting, was inversely associated with changes in BMAT; and (c) in response to high-calorie feeding, resistin levels in the marrow sera, but not the circulation, rose significantly. In addition, TNF-α expression in marrow adipocytes increased with high-calorie feeding and decreased upon fasting.CONCLUSIONHigh-calorie feeding, but not fasting, induces an immune response in bone marrow similar to what has been reported in peripheral adipose tissue. Understanding the immunomodulatory regulators in the marrow may provide further insight into the homeostatic function of this unique adipose tissue depot.FUNDINGNIH grant R24 DK084970, Harvard Catalyst/The Harvard Clinical and Translational Science Center (National Center for Advancing Translational Sciences, NIH, award UL 1TR002541), and NIH grants P30 DK040561 and U19 AG060917S1.

Calorie deprivation impairs the self-control of eating, but not of other behaviors

Objective Sustained weight loss is difficult to achieve, and weight regain is common due to biological and psychological changes caused by calorie deprivation. These changes are thought to undermine weight loss efforts by making self-control more difficult. However, there is a lack of evidence showing a causal relationship between calorie deprivation and behavioral self-control. Design In this longitudinal field experiment, we tested whether a ten-day period of calorie deprivation leads to the impairment of behavioral self-control. Participants were randomly assigned to either restrict their calorie intake or to continue eating normally for the study period. Main Outcome Measures Participants were given a box of food and non-food ‘treats’ (i.e., chocolates and lottery tickets) that they were asked to resist until the end of the study. On the last day, researchers recorded the number of treats that remained for each participant. Results Nonparametric permutation tests revealed that calorie-deprived participants ate significantly more chocolates than control participants did (p = 0.036), but that participants did not differ in the number of lottery tickets ‘scratched’ by condition (p = 0.332). Conclusion This pattern of findings suggests that calorie deprivation impairs food-related self-control, but that this self-control deficit may not generalize beyond food-related tasks.

Why market orientation matters for agriculture and fishery workers? Unravelling the association between households\u2019 occupational background and caloric deprivation in India

BackgroundDevelopmental policies in low- and middle-income countries pose immense potential within the agriculture sectors to escalate economic growth and development. Almost one-half of the workforces continue to be engaged in agriculture and allied activities with a relatively lower economic contribution than those employed in other sectors. Hence, realizing such potential however requires tremendous scaling up of skill development activities in the sector. Investing in skill development of workers engaged in agricultural and allied activities can potentially display notable value additions, income generation and therefore reductions in widespread deprivations in the form of food insecurity and undernutrition. Further with the direct link between nutrition and productivity, economic gains, it is further imperative to impart market exposure among subsistence and unskilled workers. This study therefore empirically investigates the association between households’ primary occupation and caloric deprivation in India. In particular, in a multivariate and multilevel framework, we identified how closely primary occupation of households explain the variation in caloric deprivation in India.MethodsDrawing upon data from 68th round (2011–12) of nationally representative cross-sectional Household Consumer Expenditure Survey (HCES) of National Sample Survey (NSS), Government of India, we examined the association between occupational backgrounds of households and caloric deprivation (average caloric consumption as well as low calorie intake) among Indian households.ResultsEvidences show that agricultural and fishery labor households have lowest calorie intake (2086 kcal) across all the occupational groups. However, market oriented skilled agricultural and fishery workers’ (2261 kcal – rural, 2165 kcal - urban) have higher calorie intakes than those belonging to subsistence agricultural (2165 kcal – rural, 2149 kcal - urban). Further, the multilevel logistic regression estimates suggest that in rural areas, households engaged in skilled agricultural and fishery works have significantly (at 5% level) lower odds ratio (OR: 0.72, with 95% CI: 0.63; 0.82) of having insufficient calorie intake compared to the unskilled agricultural and fishery laborer households. Estimates from variance partitioning based on multilevel logistic regression models suggest that the households’ occupational group accounts for 7 to 14% of total variation in calorie consumption.ConclusionThese insights when combined with the occupation-specific random-effects suggest that investing in skill development of agricultural and fishery workers may have immense potential to strengthen their nutritional status and to reduce deprivation levels.

Examining calorie undernourishment in India: Is it due to choice or inadequacy?

Calorie undernourishment is often associated with poverty but India presents a unique scene of decline in money-metric poverty and rise in calorie deprivation. Existing literature has varied explanation towards this effect. However, neither are the poor entirely calorie compromised nor do all the non-poor qualify calorie compliance. This is an attempt at verifying whether calorie undernourishment is a result of choice of food basket or the inadequacy of food expenditure. An answer to this question is attempted with the exploration of data obtained from the National Sample Survey Organization's Consumption Expenditure of Indian households for the periods 2004-2005 and 2011-2012. Findings reveal that over the last one decade, the average per capita per day calorie intakes have slightly increased from 2040.55 Kcal in 2004-2005 to 2087.33 Kcal in 2011-2012, which has led to the increased share of well-nourished households from 20.21% in the 61st round to 22.78% in the 68th round of survey in rural areas, whereas the similar increase in urban areas is from 36.1% to 40.65%. Calorie undernourishment among the non-poor is observed that calorie undernourishment, if any, among the non-poor is entirely due to choice but the same among the poor has a divide between choice and inadequacy. The urban poor are calorie compromised more due to choice rather than inadequacy as against their rural counterparts. With higher poverty, calorie, non-compliance among the poor is more due to choice when compared with lower magnitude of poverty. These observations form a basis for contesting the common understanding that calorie compromise is entirely driven by inadequacy/incapacity of food expenditure. could be viewed in terms of the food choices made, especially among the poor while setting the minimum threshold of food expenditure to be calorie compliant.

Diverging metabolic programmes and behaviours during states of starvation, protein malnutrition, and cachexia.

BackgroundOur evolutionary history is defined, in part, by our ability to survive times of nutrient scarcity. The outcomes of the metabolic and behavioural adaptations during starvation are highly efficient macronutrient allocation, minimization of energy expenditure, and maximized odds of finding food. However, in different contexts, caloric deprivation is met with vastly different physiologic and behavioural responses, which challenge the primacy of energy homeostasis.MethodsWe conducted a literature review of scientific studies in humans, laboratory animals, and non‐laboratory animals that evaluated the physiologic, metabolic, and behavioural responses to fasting, starvation, protein‐deficient or essential amino acid‐deficient diets, and cachexia. Studies that investigated the changes in ingestive behaviour, locomotor activity, resting metabolic rate, and tissue catabolism were selected as the focus of discussion.ResultsWhereas starvation responses prioritize energy balance, both protein malnutrition and cachexia present existential threats that induce unique adaptive programmes, which can exacerbate the caloric insufficiency of undernutrition. We compare and contrast the behavioural and metabolic responses and elucidate the mechanistic pathways that drive state‐dependent alterations in energy seeking and partitioning.ConclusionsThe evolution of energetically inefficient metabolic and behavioural responses to protein malnutrition and cachexia reveal a hierarchy of metabolic priorities governed by discrete regulatory networks.

Prolonged fasting drives a program of metabolic inflammation in human adipose tissue

ObjectiveThe human adaptive fasting response enables survival during periods of caloric deprivation. A crucial component of the fasting response is the shift from glucose metabolism to utilization of lipids, underscoring the importance of adipose tissue as the central lipid-storing organ. The objective of this study was to investigate the response of adipose tissue to a prolonged fast in humans. MethodsWe performed RNA sequencing of subcutaneous adipose tissue samples longitudinally collected during a 10-day, 0-calorie fast in humans. We further investigated observed transcriptional signatures utilizing cultured human monocytes and Thp1 cells. We examined the cellularity of adipose tissue biopsies with transmission electron microscopy and tested for associated changes in relevant inflammatory mediators in the systemic circulation by ELISA assays of longitudinally collected blood samples. ResultsCoincident with the expected shift away from glucose utilization and lipid storage, we demonstrated downregulation of pathways related to glycolysis, oxidative phosphorylation, and lipogenesis. The canonical lipolysis pathway was also downregulated, whereas fasting drove alternative lysosomal paths to lipid digestion. Unexpectedly, the dominant induced pathways were associated with immunity and inflammation, although this only became evident at the 10-day time point. Among the most augmented transcripts were those associated with macrophage identity and function, such as members of the erythroblast transformation-specific (ETS) transcription factor family. Key components of the macrophage transcriptional signal in fasting adipose tissue were recapitulated with induced expression of two of the ETS transcription factors via cultured macrophages, SPIC and SPI1. The inflammatory signal was further reflected by an increase in systemic inflammatory mediators. ConclusionsCollectively, this study demonstrates an unexpected role of metabolic inflammation in the human adaptive fasting response.

A rare case of pediatric recurrent rhabdomyolysis with compound heterogenous variants in the LPIN1

BackgroundLipin-1, encoded by LPIN1 gene, serves as an enzyme and a transcriptional co-regulator to regulate lipid metabolism and mitochondrial respiratory chain. Autosomal recessive mutations in LPIN1 were recognized as one of the most common causes of pediatric recurrent rhabdomyolysis in western countries. However, to date, there were only a few cases reported in Asian group. This study aims to report the first pediatric case of recurrent rhabdomyolysis with a novel LPIN1 mutation in China mainland in order to raise the awareness of both pediatricians and patients.Case presentationsHere we report a Chinese pediatric case of recurrent rhabdomyolysis with compound heterozygous variants (p.Arg388* and p.Arg810Cys) in the LPIN1 gene. The c.2428C > T was a novel missense variant involved Arg-to-Cys substitution at position 810 (p.Arg810Cys), located in the highly conserved region which predicted to be damaging by multiple algorithms. The patient manifested as cola-colored urine, muscle weakness and tenderness, as well as acute kidney injury with peak blood creatine kinase level 109,570 U/l in 19-month old. In his second episode of 9 years old, the symtoms were relatively milder with peak creatine kinase level 50,948 U/l. He enjoyed quite normal life between the bouts but slightly elevation of serum creatine kinase level during the fever or long-term exercises. Prolonged weight training combined with calorie deprivation were speculated to be the triggers of his illness. Prompt symptomatic therapy including fluid therapy and nutritional support was given and the patient recovered soon.ConclusionsLPIN1-related rhabdomyolysis is still quite new to physicians due to its seemly low-incidence especially in Asian countries. In the future, more active genetic test strategy and detailed prophylactic care education should be taken in patients with severe recurrent rhabdomyolysis, who are the high risk group of LPIN1 genetic defects.

Quantile Regression Analysis of Predictors of Calorie Demand in India: An Implication for Sustainable Development Goals

This study examined predictors of households’ calorie demand using consumer expenditure survey data during the time frame of millennium development goals. It draws suggestions for achieving sustainable development goals to eliminate calorie-poverty. We used the log of per-capita calorie intake as the calorie demand. Endogeneity corrected quantile regression was applied to examine the distributional effect of predictors. Findings revealed calorie-monthly per-capita consumption expenditure (MPCE) elasticities were positively statistically significant across quantiles in rural-and urban-areas, but, contrary to traditional wisdom, elasticities are lower for calorie-poor than calorie-rich households. Dietary diversification of food items, relative food price, and share of medical-and education-expenditure were the main adverse drivers of calorie demand. Our results are robust to the under-reporting and measurement error. The policy implications are: (a) only focusing on pro-poor income enhancing strategies will not able to reduce calorie deprivation, it should be backed by imparting awareness about food choice and nutritional value of low price food items, (b) to implement necessary policy to maintain stable food inflation and effectively targeted food subsidy for calorie poor, (c) to adopt forward-looking medical-and education-policy such as free health and education facilities to all by enhancing public spending to revive the quality of public hospitals and educational institutions.