Amir Zarrinpar

Time-Restricted Feeding Is a Preventative and Therapeutic Intervention against Diverse Nutritional Challenges

Because current therapeutics for obesity are limited and only offer modest improvements, novel interventions are needed. Preventing obesity with time-restricted feeding (TRF; 8-9 hr food access in the active phase) is promising, yet its therapeutic applicability against preexisting obesity, diverse dietary conditions, and less stringent eating patterns is unknown. Here we tested TRF in mice under diverse nutritional challenges. We show that TRF attenuated metabolic diseases arising from a variety of obesogenic diets, and that benefits were proportional to the fasting duration. Furthermore, protective effects were maintained even when TRF was temporarily interrupted by ad libitum access to food during weekends, a regimen particularly relevant to human lifestyle. Finally, TRF stabilized and reversed the progression of metabolic diseases in mice with preexisting obesity and type II diabetes. We establish clinically relevant parameters of TRF for preventing and treating obesity and metabolic disorders, including type II diabetes, hepatic steatosis, and hypercholesterolemia.

Diet and Feeding Pattern Affect the Diurnal Dynamics of the Gut Microbiome

The gut microbiome and daily feeding/fasting cycle influence host metabolism and contribute to obesity and metabolic diseases. However, fundamental characteristics of this relationship between the feeding/fasting cycle and the gut microbiome are unknown. Our studies show that the gut microbiome is highly dynamic, exhibiting daily cyclical fluctuations in composition. Diet-induced obesity dampens the daily feeding/fasting rhythm and diminishes many of these cyclical fluctuations. Time-restricted feeding (TRF), in which feeding is consolidated to the nocturnal phase, partially restores these cyclical fluctuations. Furthermore, TRF, which protects against obesity and metabolic diseases, affects bacteria shown to influence host metabolism. Cyclical changes in the gut microbiome from feeding/fasting rhythms contribute to the diversity of gut microflora and likely represent a mechanism by which the gut microbiome affects host metabolism. Thus, feeding pattern and time of harvest, in addition to diet, are important parameters when assessing the microbiomes contribution to host metabolism.

Review article: the emerging interplay among the gastrointestinal tract, bile acids and incretins in the pathogenesis of diabetes and non-alcoholic fatty liver disease

Recent research has led to an interest in the role of the gut and liver in type 2 diabetes mellitus (T2DM).

Do separate processes identify objects as exemplars versus members of basic-level categories? Evidence from hemispheric specialization

When an object is identified as a specific exemplar, is it analyzed differently than when it is identified at the basic level? On the basis of a previous theory, we predicted that the left hemisphere (LH) is specialized for classifying objects at the basic level and the right hemisphere (RH) is specialized for classifying objects as specific exemplars. To test this prediction, participants were asked to view lateralized pictures of animals, artifacts, and faces of famous people; immediately after each picture was presented, a label was read aloud by the computer, and the participants decided whether the label was correct for that picture. A label could name the object at either the basic level (e.g., bird) or as an exemplar (e.g., robin). As predicted, we found that basic-level labels were matched faster when pictures were presented in the right visual field (and hence encoded initially in the LH), whereas exemplar labels were matched faster when pictures were presented in the left visual field (and hence encoded initially in the RH).

Daily Eating Patterns and Their Impact on Health and Disease

Cyclical expression of cell-autonomous circadian clock components and key metabolic regulators coordinate often discordant and distant cellular processes for efficient metabolism. Perturbation of these cycles, either by genetic manipulation, disruption of light/dark cycles, or, most relevant to the human population, via eating patterns, contributes to obesity and dysmetabolism. Time-restricted feeding (TRF), during which time of access to food is restricted to a few hours, without caloric restriction, supports robust metabolic cycles and protects against nutritional challenges that predispose to obesity and dysmetabolism. The mechanism by which TRF imparts its benefits is not fully understood but likely involves entrainment of metabolically active organs through gut signaling. Understanding the relationship of feeding pattern and metabolism could yield novel therapies for the obesity pandemic.

Percutaneous Gastrostomy Device for the Treatment of Class II and Class III Obesity: Results of a Randomized Controlled Trial

Objectives:The AspireAssist System (AspireAssist) is an endoscopic weight loss device that is comprised of an endoscopically placed percutaneous gastrostomy tube and an external device to facilitate drainage of about 30% of the calories consumed in a meal, in conjunction with lifestyle (diet and exercise) counseling.Methods:In this 52-week clinical trial, 207 participants with a body-mass index (BMI) of 35.0–55.0 kg/m2 were randomly assigned in a 2:1 ratio to treatment with AspireAssist plus Lifestyle Counseling (n=137; mean BMI was 42.2±5.1 kg/m2) or Lifestyle Counseling alone (n=70; mean BMI was 40.9±3.9 kg/m2). The co-primary end points were mean percent excess weight loss and the proportion of participants who achieved at least a 25% excess weight loss.Results:At 52 weeks, participants in the AspireAssist group, on a modified intent-to-treat basis, had lost a mean (±s.d.) of 31.5±26.7% of their excess body weight (12.1±9.6% total body weight), whereas those in the Lifestyle Counseling group had lost a mean of 9.8±15.5% of their excess body weight (3.5±6.0% total body weight) (P<0.001). A total of 58.6% of participants in the AspireAssist group and 15.3% of participants in the Lifestyle Counseling group lost at least 25% of their excess body weight (P<0.001). The most frequently reported adverse events were abdominal pain and discomfort in the perioperative period and peristomal granulation tissue and peristomal irritation in the postoperative period. Serious adverse events were reported in 3.6% of participants in the AspireAssist group.Conclusions:The AspireAssist System was associated with greater weight loss than Lifestyle Counseling alone.

Serum microRNAs explain discordance of non-alcoholic fatty liver disease in monozygotic and dizygotic twins: a prospective study

Objective In the setting where two individuals are genetically similar, epigenetic mechanisms could account for discordance in the presence or absence of non-alcoholic fatty liver disease (NAFLD). This study investigated if serum microRNAs (miRs) could explain discordance in NAFLD. Design This is a cross-sectional analysis of a prospective cohort study of 40 (n=80) twin-pairs residing in Southern California. All participants underwent a standardised research visit, liver MRI using proton-density fat fraction to quantify fat content and miR profiling of their serum. Results Among the 40 twin-pairs, there were 6 concordant for NAFLD, 28 were concordant for non-NAFLD and 6 were discordant for NAFLD. The prevalence of NAFLD was 22.5% (18/80). Within the six discordant twins, a panel of 10 miRs differentiated the twin with NAFLD from the one without. Two of these miRs, miR-331-3p and miR-30c, were also among the 21 miRs that were different between NAFLD and non-NAFLD groups (for miR-331-3p: 7.644±0.091 vs 8.057±0.071, respectively, p=0.004; for miR-30c: 10.013±0.126 vs 10.418±0.086, respectively, p=0.008). Both miRs were highly heritable (35.9% and 10.7%, respectively) and highly correlated with each other (R=0.90, p=2.2×10−16) suggesting involvement in a common mechanistic pathway. An interactome analysis of these two miRs showed seven common target genes. Conclusions Using a novel human twin-study design, we demonstrate that discordancy in liver fat content between the twins can be explained by miRs, and that they are heritable.

Obesity in IBD: epidemiology, pathogenesis, disease course and treatment outcomes

Incidence of IBD is rising in parallel with overweight and obesity. Contrary to conventional belief, about 15–40% of patients with IBD are obese, which might contribute to the development of IBD. Findings from cross-sectional and retrospective cohort studies are conflicting on the effect of obesity on natural history and course of IBD. Most studies are limited by small sample size, low event rates, non-validated assessment of disease activity and lack robust longitudinal follow-up and have incomplete adjustment for confounding factors. The effect of obesity on the efficacy of IBD-related therapy remains to be studied, though data from other autoimmune diseases suggests that obesity results in suboptimal response to therapy, potentially by promoting rapid clearance of biologic agents leading to low trough concentrations. These data provide a rationale for using weight loss interventions as adjunctive therapy in patients with IBD who are obese. Obesity also makes colorectal surgery technically challenging and might increase the risk of perioperative complications. In this Review, we highlight the existing literature on the epidemiology of obesity in IBD, discuss its plausible role in disease pathogenesis and effect on disease course and treatment response, and identify high-priority areas of future research.

The circadian coordination of cell biology.

Chaix et al. review how cells generate circadian oscillations and how circadian clocks control cell biology.

Targeting Dysbiosis for the Treatment of Liver Disease

The gut microbiome is composed of a vast number of microbes in the gastrointestinal tract, which benefit host metabolism, aid in digestion, and contribute to normal immune function. Alterations in microbial composition can result in intestinal dysbiosis, which has been implicated in several diseases including obesity, inflammatory bowel disease, and liver diseases. Over the past several years, significant interactions between the intestinal microbiota and liver have been discovered, with possible mechanisms for the development as well as progression of liver disease and promising therapeutic targets to either prevent or halt the progression of liver disease. In this review the authors examine mechanisms of dysbiosis-induced liver disease; highlight current knowledge regarding the role of dysbiosis in nonalcoholic liver disease, alcoholic liver disease, and cirrhosis; and discuss potential therapeutic targets.