Important Concepts in Protein Nutrition, Aging, and Skeletal Muscle: Honoring Dr Douglas Paddon-Jones (1969-2021) by Highlighting His Research Contributions.

This review is a tribute to honor Dr Douglas Paddon-Jones by highlighting his career research contributions. Dr Paddon-Jones was a leader in recognizing the importance of muscle health and the interactions of physical activity and dietary protein for optimizing the health span. Aging is characterized by loss of muscle mass and strength associated with reduced rates of muscle protein synthesis (MPS) and the ability to repair and replace muscle proteins. Research from the team at the University of Texas Medical Branch in Galveston discovered that the age-related decline in MPS could be overcome by increasing the quantity or quality of dietary protein at each meal. Dr Paddon-Jones was instrumental in proposing and testing a "protein threshold" of ∼30 g protein/meal to optimize MPS in older adults. Dr Paddon-Jones demonstrated that physical inactivity greatly accelerates the loss of muscle mass and function in older adults. His work in physical activity led him to propose the "Catabolic Crisis Model" of muscle size and function losses, suggesting that age-related muscle loss is not a linear process, but the result of acute periods of disuse associated with injuries, illnesses, and bed rest. This model creates the opportunity to provide targeted interventions via protein supplementation and/or increased dietary protein through consuming high-quality animal-source foods. He illustrated that nutritional support, particularly enhanced protein quantity, quality, and meal distribution, can help preserve muscle health during periods of inactivity and promote health across the life course.

The T allele of TCF7L2 rs7903146 is associated with decreased glucose tolerance after bed rest in healthy older adults.

Inpatient populations are at increased risk of hyperglycemia due to factors such as medications, physical inactivity and underlying illness, which increases morbidity and mortality. Unfortunately, clinicians have limited tools available to prospectively identify those at greatest risk. We evaluated the ability of 10 common genetic variants associated with development of type 2 diabetes to predict impaired glucose metabolism. Our research model was a simulated inpatient hospital stay (7 day bed rest protocol, standardized diet, and physical inactivity) in a cohort of healthy older adults (n = 31, 65 ± 8 years) with baseline fasting blood glucose < 100 mg/dL. Participants completed a standard 75 g oral glucose tolerance test (OGTT) at baseline and post-bed rest. Bed rest increased 2-h OGTT blood glucose and insulin independent of genetic variant. In multiple regression modeling, the transcription factor 7-like 2 (TCF7L2) rs7903146 T allele predicted increases in 2-h OGTT blood glucose (p = 0.039). We showed that the TCF7L2 rs7903146 T allele confers risk for loss of glucose tolerance in nondiabetic older adults following 7 days of bed rest.

Longitudinal Analysis Evaluating Self-Reported CPAP Use for OSA during the COVID-19 Pandemic.

Continuous positive airway pressure therapy (CPAP) is a highly effective treatment for obstructive sleep apnea (OSA), but CPAP adherence remains suboptimal. The COVID-19 pandemic significantly altered sleep medicine services and aspects of daily living for sleep medicine patients, which may further compromise CPAP adherence. Sleep medicine patients were distributed an online survey at baseline and six months later (January-May 2021). Participants answered questions regarding CPAP use (any changes in CPAP use, sleep quality with CPAP use, CPAP use as advised, and changes in daily habits). Eighty-one adults completed the baseline survey, and 54 adults completed the follow-up survey. Twenty-seven participants reported a diagnosis of OSA and were prescribed CPAP (mean age 58 ± 18.2 years, 48% female, 67% Caucasian). Longitudinal analysis with chi-square association testing showed significant changes in CPAP use as advised and significant improvements in sleep quality with CPAP use when comparing the baseline to six-month follow-up survey. Additionally, logistic regression was performed to determine if pre-pandemic sleep study results (apnea-hypopnea index and respiratory disturbance index) predicted self-reported CPAP use during the pandemic, though no association was found. Throughout the pandemic, sleep medicine patients improved their CPAP use as advised and reported significant improvements in sleep quality with CPAP use.

Improvements in sleep quality and fatigue are associated with improvements in functional recovery following hospitalization in older adults.

Study objectives: Poor sleep quality, a frequent problem in older adults, has been shown to be associated with reduced physical function and wellbeing. However, little is known about the relationship between sleep quality and the recovery of physical function following hospitalization. Thus, we conducted this study to examine the association between sleep quality and functional recovery after an acute hospitalization in community dwelling older adults. Methods: Older adult patients (N = 23, mean age = 74 ± 9 years) were recruited during an acute hospitalization (average length of stay 3.9 days) with a cardiovascular (56%), pulmonary (22%), or metabolic (13%) admission diagnosis. Objective physical function was measured using the Short Physical Performance Battery (SPPB) and self-reported function was assessed with Katz Index of Independence in Activities of Daily Living (ADL) and Lawton Instrumental Activities of Daily Living Scale (IADL). Sleep quality was measured using Pittsburgh Sleep Quality Index (PSQI) global score and Iowa Fatigue Score (IFS). Testing was performed prior to discharge (baseline) and 4-weeks post-discharge (follow-up). Results: Regression models showed PSQI Subjective Sleep Quality change scores from baseline to 4-week follow-up predicted a change in ADL (ß = -0.22); PSQI Use of Sleep Medications change scores predicted a change in SPPB Total (ß = 1.62) and SPPB Chair Stand (ß = 0.63); IFS change scores predicted SPPB Total (ß = -0.16) and SPPB Chair Stand performance (ß = -0.07) change scores. Conclusions: For older adults, changes in sleep medication use, daytime dysfunction, and fatigue were associated with improvements in functional recovery (including physical performance and independence) from acute hospitalization to 4-week follow-up. These results suggest that interventions focused on improving sleep quality, daytime consequences, and fatigue might help enhance physical functioning following hospitalization. Clinical trial registration: ClinicalTrials.gov, identifier: NCT02203656.

Leucine augments specific skeletal muscle mitochondrial respiratory pathways during recovery following 7 days of physical inactivity in older adults.

In older adults, leucine mitigated the loss of insulin sensitivity associated with muscular disuse. Leucine supplementation increased mitochondrial respiration and reduced a marker of oxidative stress following periods of disuse and rehabilitation.

Practical applications of whey protein in supporting skeletal muscle maintenance, recovery, and reconditioning.

Like humans, many companion animals experience a gradual decline in skeletal muscle mass and function during later years of life. This process, analogous to sarcopenia in humans, increases risk for morbidity and mortality. Periods of reduced activity due to injury or illness, followed by an incomplete recovery, can accelerate the loss of muscle mass and function. Emerging research from human studies suggests that moderate amounts of high-quality protein may attenuate the loss of muscle, while preventing accumulation of fat during periods of disuse. Whey protein is a consumer-friendly and readily available source of high-quality protein. It supports skeletal muscle maintenance during normal aging and may also provide anabolic support during periods of illness, injury, and recovery. Ongoing research efforts continue to refine our understanding of how protein quality, quantity, and meal timing can be optimized to support retention of muscle mass and function during aging. Priority research areas include supplementation with high-quality protein during illness/injury to stimulate anabolism by targeting molecular mechanisms that regulate skeletal muscle metabolism.

The effect of acute sleep deprivation on skeletal muscle protein synthesis and the hormonal environment.

Chronic sleep loss is a potent catabolic stressor, increasing the risk of metabolic dysfunction and loss of muscle mass and function. To provide mechanistic insight into these clinical outcomes, we sought to determine if acute sleep deprivation blunts skeletal muscle protein synthesis and promotes a catabolic environment. Healthy young adults (N = 13; seven male, six female) were subjected to one night of total sleep deprivation (DEP) and normal sleep (CON) in a randomized cross-over design. Anabolic and catabolic hormonal profiles were assessed across the following day. Postprandial muscle protein fractional synthesis rate (FSR) was assessed between 13:00 and 15:00 and gene markers of muscle protein degradation were assessed at 13:00. Acute sleep deprivation reduced muscle protein synthesis by 18% (CON: 0.072 ± 0.015% vs. DEP: 0.059 ± 0.014%·h-1 , p = .040). In addition, sleep deprivation increased plasma cortisol by 21% (p = .030) and decreased plasma testosterone by 24% (p = .029). No difference was found in the markers of protein degradation. A single night of total sleep deprivation is sufficient to induce anabolic resistance and a procatabolic environment. These acute changes may represent mechanistic precursors driving the metabolic dysfunction and body composition changes associated with chronic sleep deprivation.

Countering disuse atrophy in older adults with low-volume leucine supplementation.

Older adults are at increased risk of being bedridden and experiencing negative health outcomes including the loss of muscle tissue and functional capacity. We hypothesized that supplementing daily meals with a small quantity (3-4 g/meal) of leucine would partially preserve lean leg mass and function of older adults during bed rest. During a 7-day bed rest protocol, followed by 5 days of inpatient rehabilitation, healthy older men and women (67.8 ± 1.1 yr, 14 men; 6 women) were randomized to receive isoenergetic meals supplemented with leucine (LEU, 0.06 g/kg/meal; n = 10) or an alanine control (CON, 0.06 g/kg/meal; n = 10). Outcomes were assessed at baseline, following bed rest, and after rehabilitation. Body composition was measured by dual-energy X-ray absorptiometry. Functional capacity was assessed by knee extensor isokinetic and isometric dynamometry, peak aerobic capacity, and the short physical performance battery. Muscle fiber type, cross-sectional area, signaling protein expression levels, and single fiber characteristics were determined from biopsies of the vastus lateralis. Leucine supplementation reduced the loss of leg lean mass during bed rest (LEU vs. CON: -423 vs. -1035 ± 143 g; P = 0.008) but had limited impact on strength or endurance-based functional outcomes. Similarly, leucine had no effect on markers of anabolic signaling and protein degradation during bed rest or rehabilitation. In conclusion, providing older adults with supplemental leucine has minimal impact on total energy or protein consumption and has the potential to partially counter some, but not all, of the negative effects of inactivity on muscle health.NEW & NOTEWORTHY Skeletal muscle morphology and function in older adults was significantly compromised by 7 days of disuse. Leucine supplementation partially countered the loss of lean leg mass but did not preserve muscle function or positively impact changes at the muscle fiber level associated with bed rest or rehabilitation. Of note, our data support a relationship between myonuclear content and adaptations to muscle atrophy at the whole limb and single fiber level.

Improving Dietary Protein Quality Reduces the Negative Effects of Physical Inactivity on Body Composition and Muscle Function.

BACKGROUND: Brief periods of physical inactivity can compromise muscle health. Increasing dietary protein intake is potentially beneficial but complicated by difficulties reconciling anabolic potential with a realistic food volume and energy intake. We sought to determine whether increasing dietary protein quality could reduce the negative effects of physical inactivity. METHODS: Twenty healthy, older men and women completed 7 days of bed rest followed by 5 days of rehabilitation. Volunteers consumed a mixed macronutrient diet (MIXED: N = 10; 68 ± 2 years; 1,722 ± 29 kcal/day; 0.97 ± 0.01 g protein/kg/day) or an isoenergetic, whey-augmented, higher protein quality diet (WHEY: N = 10; 69 ± 1 years; 1,706 ± 23 kcal/day; 0.90 ± 0.01 g protein/kg/day). Outcomes included body composition, blood glucose, insulin, and a battery of physical function tests. RESULTS: During bed rest, both groups experienced a 20% reduction in knee extension peak torque (p < .05). The WHEY diet partially protected leg lean mass (-1,035 vs. -680 ± 138 g, MIXED vs. WHEY; p = .08) and contributed to a greater loss of body fat (-90 vs. -233 ± 152 g, MIXED vs. WHEY; p < .05). Following rehabilitation, knee extension peak torque in the WHEY group fully recovered (-10.0 vs. 2.2 ± 4.1 Nm, MIXED vs. WHEY; p = .05). Blood glucose, insulin, aerobic capacity, and Short Physical Performance Battery (SPPB) changes were similar in both dietary conditions (p > .05). CONCLUSIONS: Improving protein quality without increasing total energy intake has the potential to partially counter some of the negative effects of bed rest in older adults.

2,000 Steps/Day Does Not Fully Protect Skeletal Muscle Health in Older Adults During Bed Rest.

Physical activity in an inpatient setting is often limited to brief periods of walking. For healthy adults, public health agencies recommend a minimum of 150 min/week of moderate-intensity exercise. The authors sought to determine if meeting this activity threshold, in the absence of incidental activities of daily living, could protect skeletal muscle health during bed rest. Healthy older adults (68 ± 2 years) were randomized to 7-day bed rest with (STEP, n = 7) or without (CON, n = 10) a 2,000 steps/day intervention. Performing 2018 ± 4 steps/day did not prevent the loss of lean leg mass and had no beneficial effect on aerobic capacity, strength, or muscle fiber volume. However, the insulin response to an oral glucose challenge was preserved. Performing a block of 2,000 steps/day, in the absence of incidental activities of daily living, was insufficient to fully counter the catabolic effects of bed rest in healthy older adults.

11C-L-methyl methionine dynamic PET/CT of skeletal muscle: response to protein supplementation compared to L-[ring 13C6] phenylalanine infusion with serial muscle biopsy.

OBJECTIVE: The objective of this study was to determine if clinical dynamic PET/CT imaging with 11C-L-methyl-methionine (11C-MET) in healthy older women can provide an estimate of tissue-level post-absorptive and post-prandial skeletal muscle protein synthesis that is consistent with the more traditional method of calculating fractional synthesis rate (FSR) of muscle protein synthesis from skeletal muscle biopsies obtained during an infusion of L-[ring 13C6] phenylalanine (13C6-Phe). METHODS: Healthy older women (73 ± 5 years) completed both dynamic PET/CT imaging with 11C-MET and a stable isotope infusion of 13C6-Phe with biopsies to measure the skeletal muscle protein synthetic response to 25 g of a whey protein supplement. Graphical estimation of the Patlak coefficient Ki from analysis of the dynamic PET/CT images was employed as a measure of incorporation of 11 C-MET in the mid-thigh muscle bundle. RESULTS: Post-prandial values [mean ± standard error of the mean (SEM)] were higher than post-absorptive values for both Ki (0.0095 ± 0.001 vs. 0.00785 ± 0.001 min-1, p < 0.05) and FSR (0.083 ± 0.008 vs. 0.049 ± 0.006%/h, p < 0.001) in response to the whey protein supplement. The percent increase in Ki and FSR in response to the whey protein supplement was significantly correlated (r = 0.79, p = 0.015). CONCLUSIONS: Dynamic PET/CT imaging with 11C-MET provides an estimate of the post-prandial anabolic response that is consistent with a traditional, invasive stable isotope, and muscle biopsy approach. These results support the potential future use of 11C-MET imaging as a non-invasive method for assessing conditions affecting skeletal muscle protein synthesis.

Maternal high fructose and low protein consumption during pregnancy and lactation share some but not all effects on early-life growth and metabolic programming of rat offspring.

Maternal nutritional stress during pregnancy acts to program offspring metabolism. We hypothesized that the nutritional stress caused by maternal fructose or low protein intake during pregnancy would program the offspring to develop metabolic aberrations that would be exacerbated by a diet rich in fructose or fat during adult life. The objective of this study was to characterize and compare the fetal programming effects of maternal fructose with the established programming model of a low-protein diet on offspring. Male offspring from Sprague-Dawley dams fed a 60% starch control diet, a 60% fructose diet, or a low-protein diet throughout pregnancy and lactation were weaned onto either a 60% starch control diet, 60% fructose diet, or a 30% fat diet for 15 weeks. Offspring from low-protein and fructose-fed dam showed retarded growth (P<.05) at weaning (50.3, 29.6 vs 59.1±0.8 g) and at 18 weeks of age (420, 369 vs 464±10.9 g). At 18 weeks of age, offspring from fructose dams expressed greater quantities (P<.05) of intestinal Pgc1a messenger RNA compared with offspring from control or low-protein dams (1.31 vs 0.89, 0.85; confidence interval, 0.78-1.04). Similarly, maternal fructose (P=.09) and low-protein (P<.05) consumption increased expression of Pgc1a in offspring liver (7.24, 2.22 vs 1.22; confidence interval, 2.11-3.45). These data indicate that maternal fructose feeding is a programming model that shares some features of maternal protein restriction such as retarded growth, but is unique in programming of selected hepatic and intestinal transcripts.

Erythropoietin Does Not Enhance Skeletal Muscle Protein Synthesis Following Exercise in Young and Older Adults.

PURPOSE: Erythropoietin (EPO) is a renal cytokine that is primarily involved in hematopoiesis while also playing a role in non-hematopoietic tissues expressing the EPO-receptor (EPOR). The EPOR is present in human skeletal muscle. In mouse skeletal muscle, EPO stimulation can activate the AKT serine/threonine kinase 1 (AKT) signaling pathway, the main positive regulator of muscle protein synthesis. We hypothesized that a single intravenous EPO injection combined with acute resistance exercise would have a synergistic effect on skeletal muscle protein synthesis via activation of the AKT pathway. METHODS: Ten young (24.2 ± 0.9 years) and 10 older (66.6 ± 1.1 years) healthy subjects received a primed, constant infusion of [ring-13C(6)] L-phenylalanine and a single injection of 10,000 IU epoetin-beta or placebo in a double-blind randomized, cross-over design. 2 h after the injection, the subjects completed an acute bout of leg extension resistance exercise to stimulate skeletal muscle protein synthesis. RESULTS: Significant interaction effects in the phosphorylation levels of the members of the AKT signaling pathway indicated a differential activation of protein synthesis signaling in older subjects when compared to young subjects. However, EPO offered no synergistic effect on vastus lateralis mixed muscle protein synthesis rate in young or older subjects. CONCLUSIONS: Despite its ability to activate the AKT pathway in skeletal muscle, an acute EPO injection had no additive or synergistic effect on the exercise-induced activation of muscle protein synthesis or muscle protein synthesis signaling pathways.

Protecting Skeletal Muscle with Protein and Amino Acid during Periods of Disuse.

Habitual sedentary behavior increases risk of chronic disease, hospitalization and poor quality of life. Short-term bed rest or disuse accelerates the loss of muscle mass, function, and glucose tolerance. Optimizing nutritional practices and protein intake may reduce the consequences of disuse by preserving metabolic homeostasis and muscle mass and function. Most modes of physical inactivity have the potential to negatively impact the health of older adults more than their younger counterparts. Mechanistically, mammalian target of rapamycin complex 1 (mTORC1) signaling and muscle protein synthesis are negatively affected by disuse. This contributes to reduced muscle quality and is accompanied by impaired glucose regulation. Simply encouraging increased protein and/or energy consumption is a well-intentioned, but often impractical strategy to protect muscle health. Emerging evidence suggests that leucine supplemented meals may partially and temporarily protect skeletal muscle during disuse by preserving anabolism and mitigating reductions in mass, function and metabolic homeostasis.

Leucine partially protects muscle mass and function during bed rest in middle-aged adults.

BACKGROUND: Physical inactivity triggers a rapid loss of muscle mass and function in older adults. Middle-aged adults show few phenotypic signs of aging yet may be more susceptible to inactivity than younger adults. OBJECTIVE: The aim was to determine whether leucine, a stimulator of translation initiation and skeletal muscle protein synthesis (MPS), can protect skeletal muscle health during bed rest. DESIGN: We used a randomized, double-blind, placebo-controlled trial to assess changes in skeletal MPS, cellular signaling, body composition, and skeletal muscle function in middle-aged adults (n = 19; age ± SEM: 52 ± 1 y) in response to leucine supplementation (LEU group: 0.06 g ∙ kg(-1) ∙ meal(-1)) or an alanine control (CON group) during 14 d of bed rest. RESULTS: Bed rest decreased postabsorptive MPS by 30% ± 9% (CON group) and by 10% ± 10% (LEU group) (main effect for time, P < 0.05), but no differences between groups with respect to pre-post changes (group × time interactions) were detected for MPS or cell signaling. Leucine protected knee extensor peak torque (CON compared with LEU group: -15% ± 2% and -7% ± 3%; group × time interaction, P < 0.05) and endurance (CON compared with LEU: -14% ± 3% and -2% ± 4%; group × time interaction, P < 0.05), prevented an increase in body fat percentage (group × time interaction, P < 0.05), and reduced whole-body lean mass loss after 7 d (CON compared with LEU: -1.5 ± 0.3 and -0.8 ± 0.3 kg; group × time interaction, P < 0.05) but not 14 d (CON compared with LEU: -1.5 ± 0.3 and -1.0 ± 0.3 kg) of bed rest. Leucine also maintained muscle quality (peak torque/kg leg lean mass) after 14 d of bed-rest inactivity (CON compared with LEU: -9% ± 2% and +1% ± 3%; group × time interaction, P < 0.05). CONCLUSIONS: Bed rest has a profoundly negative effect on muscle metabolism, mass, and function in middle-aged adults. Leucine supplementation may partially protect muscle health during relatively brief periods of physical inactivity. This trial was registered at clinicaltrials.gov as NCT00968344.

Fourteen days of bed rest induces a decline in satellite cell content and robust atrophy of skeletal muscle fibers in middle-aged adults.

Bed rest, a ground-based spaceflight analog, induces robust atrophy of skeletal muscle, an effect that is exacerbated with increasing age. We examined the effect of 14 days of bed rest on skeletal muscle satellite cell content and fiber type atrophy in middle-aged adults, an understudied age demographic with few overt signs of muscle aging that is representative of astronauts who perform long-duration spaceflight. Muscle biopsies were obtained from the vastus lateralis of healthy middle-aged adults [n= 7 (4 male, 3 female); age: 51 ± 1 yr] before (Pre-BR) and after (Post-BR) 14 days of bed rest. Immunohistochemical analyses were used to quantify myosin heavy chain (MyHC) isoform expression, cross-sectional area (CSA), satellite cell and myonuclear content, and capillary density. Peak oxygen consumption, knee extensor strength, and body composition were also measured Pre-BR and Post-BR. Post-BR MyHC type 2a fiber percentage was reduced, and mean CSA decreased in all fiber types (-24 ± 5%;P< 0.05). Satellite cell content was also reduced Post-BR (-39 ± 9%;P< 0.05), and the change in satellite cell content was significantly correlated with the change in mean fiber CSA (r(2)= 0.60;P< 0.05). A decline in capillary density was observed Post-BR (-23 ± 6%;P< 0.05), and Post-BR capillary content was significantly associated with Post-BR peak aerobic capacity (r(2)= 0.59;P< 0.05). A subtle decline in myonuclear content occurred during bed rest (-5 ± 1%;P< 0.05). The rapid maladaptation of skeletal muscle to 14 days of mechanical unloading in middle-aged adults emphasizes the need for robust countermeasures to preserve muscle function in astronauts.

Protein: A nutrient in focus.

Protein is an essential component of a healthy diet and is a focus of research programs seeking to optimize health at all stages of life. The focus on protein as a nutrient often centers on its thermogenic and satiating effect, and when included as part of a healthy diet, its potential to preserve lean body mass. A growing body of literature, including stable isotope based studies and longer term dietary interventions, suggests that current dietary protein recommendations may not be sufficient to promote optimal muscle health in all populations. A protein intake moderately higher than current recommendations has been widely endorsed by many experts and working groups and may provide health benefits for aging populations. Further, consuming moderate amounts of high-quality protein at each meal may optimally stimulate 24-h muscle protein synthesis and may provide a dietary platform that favors the maintenance of muscle mass and function while promoting successful weight management in overweight and obese individuals. Dietary protein has the potential to serve as a key nutrient for many health outcomes and benefits might be increased when combined with adequate physical activity. Future studies should focus on confirming these health benefits from dietary protein with long-term randomized controlled studies.

Impact of excess gestational and post-weaning energy intake on vascular function of swine offspring.

BACKGROUND: The development of long-term vascular disease can be linked to the intrauterine environment, and maternal nutrition during gestation plays a critical role in the future vascular health of offspring. The purpose of this investigation was to test the hypothesis that a high-energy (HE) gestational diet, HE post-weaning diet, or their combination will lead to endothelial dysfunction in offspring. METHODS: Duroc × Landrace gilts (n = 16) were assigned to either a HE (10,144 Kcal/day, n = 8) or normal energy (NE: 6721 Kcal/day, n = 8) diet throughout pregnancy. Piglets were placed on either a NE or HE diet during the growth phase. At 3 months of age femoral arteries were harvested from offspring (n = 47). Endothelial-dependent and -independent vasorelaxation was measured utilizing wire-myography and increasing concentrations of bradykinin (BK) and sodium nitroprusside (SNP), respectively. RESULTS: BK and SNP induced vasorelaxation were significantly reduced in the femoral arteries of gestational HE offspring. However, no effect for the post-weaning diet on BK and SNP induced vasorelaxation was seen. This investigation demonstrates that a HE diet prenatally diminishes both BK and SNP induced vasorelaxation in swine. CONCLUSIONS: These findings suggest that a HE gestational diet can play a critical role in the development of offspring's vascular function, predisposing them to endothelial dysfunction. This dysfunction may lead to atherosclerotic disease development later in life.

Excess pregnancy weight gain leads to early indications of metabolic syndrome in a swine model of fetal programming.

Few data exist on the impact of maternal weight gain on offspring despite evidence demonstrating that early-life environment precipitates risks for metabolic syndrome. We hypothesized that excessive weight gain during pregnancy results in programming that predisposes offspring to obesity and metabolic syndrome. We further hypothesized that early postweaning nutrition alters the effects of maternal weight gain on indications of metabolic syndrome in offspring. Pregnant sows and their offspring were used for these experiments due to similarities with human digestive physiology, metabolism, and neonatal development. First parity sows fed a high-energy (maternal nutrition high energy [MatHE]) diet gained 12.4 kg (42%) more weight during pregnancy than sows fed a normal energy (maternal nutrition normal energy) diet. Birth weight and litter characteristics did not differ, but offspring MatHE gilts weighed more (P < .05) at age of 3 weeks (4.35 vs 5.24 ± 0.35 kg). At age of 12 weeks, offspring from MatHE mothers that were weaned onto a high-energy diet had elevated (P < .05) blood glucose (102 vs 64 mg/dL, confidence interval [CI]: 67-91), insulin (0.21 vs 0.10 ng/mL, CI: 0.011-0.019), and lower nonesterified fatty acid (0.31 vs 0.62 mmol/L, CI: 0.34-0.56) than offspring from the same MatHE sows weaned to the normal energy diet. These effects were not observed for offspring from sows fed a normal energy diet during pregnancy. These data indicate that excessive gestational weight gain during pregnancy in a pig model promotes early indications of metabolic syndrome in offspring that are further promoted by a high-energy postweaning diet.